Effects of ivabradine therapy on heart failure biomarkers.

BACKGROUND: Heart rate (HR) reduction is associated with improved outcomes in patients with heart failure (HF) and biomarkers can be a valuable diagnostic tool in HF management. The primary aim of our study was to evaluate the short-term (6 months) effect of ivabradine on N-terminal pro B-type natriuretic peptide (NT-proBNP), CA-125, and cystatin-C values in systolic HF outpatients, and secondary aim was to determine the relationship between baseline HR and the NT-proBNP, CA-125, cystatin-C, and clinical status variation with ivabradine therapy. METHODS: Ninety-eight patients (mean age: 65.81 ± 10.20 years; 33 men), left ventricular ejection fraction < 35% with Simpson method, New York Heart Association (NYHA) class II-III, sinus rhythm and resting HR > 70/min, optimally treated before the study were included. Among them, two matched groups were formed: the ivabradine group and the control group. Patients received ivabradine with an average (range of 10-15) mg/day during 6 months of follow-up. Blood samples for NT-proBNP, CA-125, and cystatin-C were taken at baseline and at the end of a 6-month follow-up in both groups. RESULTS: There was a significant decrease in NYHA class in the ivabradine group (2.67 ± ± 0.47 vs. 1.85 ± 0.61, p < 0.001). When ivabradine and control groups were compared, a significant difference was also found in NHYA class 6 months later (p = 0.013). A significant decrease was found in HR in the ivabradine and control groups (84.10 ± 8.76 vs. 68.36 ± ± 8.32 bpm, p = 0.001; 84.51 ± 10 vs. 80.40 ± 8.3 bpm, p = 0.001). When both groups were compared, a significant difference was also found in HR after 6 months (p = 0.001). A significant decrease was found in cystatin-C (2.10 ± 0.73 vs. 1.50 ± 0.44 mg/L, p < 0.001), CA-125 (30.09 ± 21.08 vs. 13.22 ± 8.51 U/mL, p < 0.001), and NT-proBNP (1,353.02 ± 1,453.77 vs. 717.81 ± 834.76 pg/mL, p < 0.001) in the ivabradine group. When ivabradine and control groups were compared after 6 months, a significant decrease was found in all HF parameters (respectively; cystatin-C: p = 0.001, CA-125: p = 0.001, NT-proBNP: p = 0.001). Creatinine level was significantly decreased and glomerular filtration rate (GFR) was significantly increased in the ivabradine group (1.02 ± 0.26 vs. 0.86 ± 0.17, creatinine: p = 0.001; 79.26 ± 18.58 vs. 92.48 ± 19.88, GFR: p = 0.001). There was no significant correlation between NYHA classes (before and after ivabradine therapy) and biochemical markers, or HR. CONCLUSIONS: In the outpatients with systolic HF, persistent resting HF > 70/min with optimal medical therapy, the NT-proBNP, CA-125, and cystatin-C reductions were obtained with ivabradine treatment. Measurement of NT-proBNP, CA-125, and cystatin-C may prove to be useful in biomarker panels evaluating ivabradine therapy response in HF patients.

Myocardial performance index in patients with dipper and nondipper hypertension.

BACKGROUND: The aim of this study was to evaluate the relationship between left ventricular (LV) myocardial performance index (MPI) and nondipper pattern in hypertensive patients. METHODS: Between June 2012 and November 2012, patients admitted to the Cardiology Department of Düzce University Faculty of Medicine and diagnosed previously with essential hypertension were included in the study. Patients were divided into two groups, nondippers and dippers, using ambulatory blood pressure measurement. All patients were evaluated by two-dimensional and Doppler echocardiography. LV MPI was calculated from tissue Doppler imaging parameters. RESULTS: There was no significant difference between the two groups in the proportion of each class of antihypertensive medications. Dippers and nondippers had similar age, BMI, lipid profiles, and smoking status. The MPI value was significantly higher in nondippers than in dippers, and was correlated negatively with the rate of systolic and diastolic blood pressure fall at night (P<0.001). CONCLUSION: Our study showed that MPI is disturbed in patients with nondipper hypertension. MPI may be used in the diagnosis and follow-up of global LV dysfunction in patients with a nondipper pattern, but further prospective studies are needed.

Carbohydrate antigen-125 and N-terminal pro-brain natriuretic peptide levels: compared in heart-failure prognostication.

Carbohydrate antigen-125 (CA-125) is emerging as a prognostic biomarker of risk in heart failure. In a prospective study, we compared the prognostic values of CA-125 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable heart failure.We enrolled 102 consecutive chronic, stable, systolic-heart-failure patients (68 men and 34 women; median age, 71 yr) from November 2008 through February 2010. We measured baseline NT-proBNP and CA-125 levels and compared their prognostic values. The primary endpoint was all-cause death and other major adverse events, defined as hospitalization for decompensated heart failure or acute coronary syndrome.During a mean follow-up period of 14 ± 2 months, 12 patients died and 35 others sustained major adverse events. We found that CA-125 level significantly correlated with New York Heart Association functional class, pulmonary artery pressure, microalbuminuria, creatine kinase-MB fraction, and hemoglobin, albumin, and NT-proBNP levels. Upon receiver operating characteristic curve analysis, CA-125 and NT-proBNP had similar accuracy in predicting major adverse events and death: for major adverse events, area under the curve (AUC) was 0.699 for CA-125 (P=0.002) and 0.696 for NT-proBNP (P=0.002); for death, AUC was 0.784 for CA-125 (P=0.003) and 0.824 for NT-proBNP (P=0.001). Multivariate Cox regression analysis showed that CA-125 levels greater than 32 U/mL and NT-proBNP levels greater than 5,300 pg/mL had independent prognostic value for major adverse events and death.We conclude that baseline CA-125 and NT-proBNP levels are comparably reliable as heart-failure markers, and that CA-125 can be used for prognosis prediction in heart failure.

Cystatin C levels in patients with dipper and nondipper hypertension.

OBJECTIVE: Subjects with nondipper hypertension carry a higher risk of cardiovascular events than their normotensive counterparts. The present study was designed to investigate cystatin C levels in patients with dipper and nondipper hypertension. METHODS: Eighty-eight consecutive patients who had been treated with antihypertensive drugs for at least 6 months were included in the study. Dipping and nondipping patterns were detected with ambulatory blood pressure monitoring. Clinical, laboratory, and ambulatory blood pressure monitoring data of patient groups with nondipper and dipper hypertension were compared. RESULTS: Patients in the nondipper group were older than those in the dipper group. Serum cystatin C level was higher in the patients in the nondipper group. Cystatin C was negatively correlated with the rate of systolic blood pressure fall at night (r = -0.41; P < 0.001). Linear regression analyses revealed that only cystatin C level was a significant correlate of nocturnal systolic blood pressure decrease. Logistic regression analyses also showed that cystatin C was an independent predictor of nondipping pattern (odds ratio, 3.586; 95% confidence interval, 1.432-8.98; P = 0.006]). CONCLUSION: The present study showed that cystatin C is higher in patients with nondipper hypertension patients.

Performance of bioelectrical impedance analysis in the diagnosis of metabolic syndrome.

OBJECTIVE: Central obesity is a prerequisite for the diagnosis of metabolic syndrome (MetS). Precise measurement of visceral fat by bioelectrical impedance analysis (BIA) has been validated. The aim of this study was to investigate the diagnostic performance of BIA in MetS and validate the best cutoff in a large adult cohort. MATERIALS AND METHODS: The study was performed on the MELEN Study cohort-a prospectively designed survey on the prevalence of cardiometabolic risk factors in Turkish adults. The final cohort consisted of 2219 participants. Weight and visceral body composition were measured without shoes in light indoor clothes using a bioimpedance analyzer (Omron BF 510; Omron Corp, Kyoto, Japan). Plasma concentrations of cholesterol, insulin, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and other biochemical variables were measured. The diagnostic performance of visceral fat measurement by BIA in patients with MetS was assessed. RESULTS: Metabolic syndrome was detected in 751 participants (520 women and 231 men with a mean age of 55 [12] years; 34% of the whole study population). Total body fat and visceral fat levels were higher in subjects with MetS. Correlation analyses showed that there were significant correlations between anthropometric and BIA measurements. Receiver operating curve characteristics of visceral adiposity revealed the best cutoff values as greater than 12% for men and greater than 9% for women. The diagnostic performance was good in both sexes (the sensitivity/specificity and area-under-the-curve values were 76%/75% and 0.83 for men and 83%/67% and 0.81 for women, respectively). CONCLUSIONS: Visceral fat measured with BIA is an easily applicable and useful method for identifying people with MetS. The best cutoff values were higher than 12% for men and higher than 9% for women.

Efficacy of olmesartan therapy on fibrinolytic capacity in patients with hypertension.

The efficacy of olmesartan on fibrinolytic capacity has not been studied yet. Therefore, the aim of the present study was to investigate the efficacy of olmesartan on hemostatic/fibrinolytic status by measuring plasma level of plasminogen activator inhibitor-1 (PAI-1) and soluble thrombomodulin levels in patients with hypertension. Forty-two consecutive, newly diagnosed (25 women and 17 men with a mean age of 48 ± 8 years) patients with untreated essential hypertension were included in the study. Olmesartan medoxomil (20 mg/day) was started and the patients were followed up for 6 months. Baseline biochemical variables, thrombomodulin, and PAI-1 levels were compared with the levels of these variables measured at the end of the 6-month follow-up period. After 6 months of treatment with olmesartan medoxomil, there was a significant reduction in systolic and diastolic blood pressure (from 159.5 ± 10.9 to 134.6 ± 12.7 mmHg and from 98.0 ± 6.3 to 83.9 ± 7.0 mmHg, respectively). Mean plasma PAI-1 and thrombomodulin levels were also significantly decreased (59.73 ± 41.91 vs. 48.60 ± 33.65 ng/ml, P = 0.001 and 8.09 ± 2.29 vs. 6.92 ± 1.42 µg/l, P < 0.001, respectively). Olmesartan medoxomil decreased plasma PAI-1 and thrombomodulin levels after 6 months of therapy, indicating a favorable effect on fibrinolytic capacity in patients with essential hypertension.

The prognostic value of mean platelet volume in decompensated heart failure.

BACKGROUND: Congestive heart failure (CHF) is a major public health problem that is related to substantial morbidity, impaired quality of life and diminished survival. Mean platelet volume (MPV) is an indicator of platelet activation. AIM: To investigate whether there is a difference of MPV in patients with decompensated and stable heart failure (SHF), and test the prognostic value of MPV in decompensated heart failure (DHF). METHODS: 136 consecutive patients with DHF were enrolled. 71 with SHF were also enrolled for comparison. Patients were followed up for a mean of 18±12 months. The primary endpoint was death from any cause. Clinical characteristics of patients with DHF who died during follow-up were compared with the those of the survivors. RESULTS: MPV was significantly higher in DHF group than in the SHF group. 71 patients died during the follow-up period (18±12 months). Comparison with survivors revealed that mortality was associated with age, systolic blood pressure, pulmonary artery pressure, serum creatinine, urea and MPV. MPV was determined as an independent risk factor for mortality (OR 1.553, 95% CI 1.024 to 2.354, p=0.038). Receiver operating characteristic analysis showed that MPV level on admission was a predictor of mortality (area under the curve (AUC) for in-hospital mortality was 0.716 (95% CI 0.632 to 0.789, p=0.003) and AUC for 6-month mortality was 0.815 (95% CI 0.74 to 0.877, p<0.001), respectively). CONCLUSION: MPV is increased in patients with DHF. Also, MPV on admission is an independent predictor of in-hospital mortality and 6-month mortality.

Pioglitazone improves ventricular diastolic function in patients with diabetes mellitus: a tissue Doppler study.

OBJECTIVE: Pioglitazone treatment in type 2 diabetes mellitus produced significant improvements in glycaemic control, plasma lipids, blood pressure and inflammation. The aim of this study was to investigate the effect of pioglitazone on systolic and diastolic function in diabetic patients. METHODS AND RESULTS: Forty-nine diabetic patients were included in the study. The patients had never received thiazolidinedione therapy before. Clinical and echocardiographic variables were measured. 30 mg pioglitazone were administered. The patients were followed up for six months and all the measurements were re-evaluated for comparison. Body mass index (BMI) significantly increased after treatment. Fasting glucose, HbA1c and systolic blood pressure decreased. Insulin resistance improved and the HOMA-IR index decreased after pioglitazone treatment. Mean aortic diameter, left atrial systolic and diastolic volumes significantly decreased after therapy. Among diastolic function variables mitral E wave, E/A, ejection time and pulmonary vein peak reverse flow velocity (PVA) significantly increased whereas isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT), deceleration time, E/E' and pulmonary vein late systolic flow (PVS2) decreased after pioglitazone therapy. Among tissue Doppler variables early (E) ventricular inflow velocities measured from the tricuspid lateral annulus, the mitral septal and lateral annulus, the anterior, inferior and posterior free wall significantly increased. Late (A) ventricular inflow velocities measured from the anterior, inferior free wall and the mitral septal annulus also increased. CONCLUSION: Pioglitazone treatment in type 2 diabetes mellitus produced significant improvements in measures of glycaemic control and diastolic ventricular function.

Efficacy of short-term high-dose atorvastatin for prevention of contrast-induced nephropathy in patients undergoing coronary angiography.

Contrast-induced nephropathy (CIN) is associated with increased morbidity, extended hospital stay, and higher costs. We compared an atorvastatin plus N-acetylcysteine (NAC) regimen with NAC alone in patients undergoing coronary angiography. A total of 130 patients (mean age 54 +/- 10; 77 men) undergoing coronary angiography were studied. Seven CIN cases occurred in the NAC group and 2 in the atorvastatin + NAC group; this difference was not significant. Baseline mean creatinine and estimated glomerular filtration rate (eGFR) were similar between the 2 groups, whereas after the procedure there was a significant creatinine decrease and eGFR increase in the atorvastatin + NAC group. Change in creatinine (baseline creatinine-creatinine after the procedure) was also significantly higher in patients taking statin plus NAC. Atorvastatin may be effective in protecting patients undergoing coronary angiography from CIN.

Outcome of primary percutaneous intervention in patients with infarct-related coronary artery ectasia.

Data related to the incidence and clinical outcome of acute myocardial infarction (AMI) in patients with preexisting coronary artery ectasia (CAE) are limited. We assessed whether infarct-related artery ectasia (EIRA) indicates an untoward clinical outcome in patients with AMI undergoing primary percutaneous coronary intervention (pPCI). Consecutive patients (n = 643) who presented with AMI and were treated with pPCI were analyzed retrospectively; 31 patients (4.8%) had EIRA. Patients who had EIRA were significantly younger and had higher incidence of hypertension, previous stroke, smoking, inferior wall AMI, and Killip score >1. Infarct-related artery ectasia was more frequent in the right coronary artery (RCA). Impaired epicardial arterial flow, thrombus burden score of infarct-related artery (IRA), impaired Thrombolysis in Myocardial Infarction (TIMI) Myocardial Perfusion Grade, and distal embolization were significantly higher whereas ST-segment resolution and collateral vascular development were significantly lower in patients with EIRA. Infarct-related artery ectasia was an independent predictor of adverse outcome (odds ratio: 0.197; 95% confidence interval [CI]: 0.062-0.633; P = .006).

A case of acute stent thrombosis treated successfully with intracoronary tirofiban.

Acute stent thrombosis (AST) is occasionally observed during percutaneous coronary intervention in patients with acute coronary syndrome (ACS). It may jeopardize hemodynamic status. Currently, there is no adequate solution for this problem. We report our experience with an ACS patient who developed AST associated with cardiogenic shock after percutaneous coronary stent deployment. Intracoronary administration of tirofiban immediately restored the coronary flow of the target vessel, and the disastrous condition was reversed. Our experience suggests that intracoronary administration of tirofiban can be considered as an option in cases of AST during percutaneous coronary intervention.

The effect of non-dipper pattern of hypertension on erectile dysfunction.

BACKGROUND: The purpose of this study was to evaluate the relationship between erectile dysfunction (ED) and non-dipper pattern in hypertensive patients. METHODS: A total of 750 consecutive patients with essential hypertension, who had been evaluated with ambulatory BP monitoring, were screened for this study. One hundred and thirty-two male patients (age range 28-54 years) who had fulfilled the inclusion and exclusion criteria were included in the final analysis. Dipper and non-dipper patterns were detected and sexual function was assessed by the self-administered questionnaire of the International Index of Erectile Function (IIEF). RESULTS: There was no significant difference between the two groups regarding the number of medications taken and the proportion of each class of antihypertensive medications. Mean age, body mass index, lipid profiles, rate of smoking were similar between the two groups. IIEF score was significantly higher in non-dippers than dippers (p= 0.009). Non-dipping was also found to be an independent determinant for ED. CONCLUSION: The result of the present study further suggests that non-dipping is a risk indicator for early deterioration of erectile function in hypertensive patients.

Mean platelet volume in patients with dipper and non-dipper hypertension.

Patients with non-dipper hypertension are known to carry a high risk of cardiovascular complications. In this study, we hypothesized that non-dippers may be associated with platelet dysfunction and it can be determined by mean platelet volume (MPV). A total of 216 outpatients treated with antihypertensive drugs for at least 6 months were enrolled. Dipper and non-dipper patterns were detected and clinical, laboratory and ambulatory blood pressure recording data were matched between non-dipping and dipping groups. MPV was significantly higher in patients in non-dipping than dipping groups (p<0.001). In correlation analyses, MPV was negatively correlated with the rate of systolic and diastolic fall at night (p<0.001, r=-0.46) and (p<0.001, r=-0.43), respectively. Also MPV was correlated with nocturnal pulse pressure (p=0.001, r=0.22). Other variables were similar between non-dipping and dipping groups. The present study showed that MPV is higher in non-dipping than dipping hypertensive patients. Platelet activation or dysfunction probably is an alternative mechanism for increasing cardiovascular events in non-dippers.

Efficacy of nebivolol on flow-mediated dilation in patients with slow coronary flow.

Slow coronary flow (SCF) is the phenomenon of slow progression of angiographic contrast in the coronary arteries in the absence of stenosis in the epicardial vessels in some patients presenting with chest pain. There are no definite treatment modalities for patients with SCF. Our aim was to investigate the efficacy of nebivolol in patients with slow coronary flow by monitoring its effects on endothelial function and different markers of inflammation. Forty-two patients (16 females, 26 males; mean age, 55 +/- 10) with slow coronary flow (SCF) were included in the study. After baseline assessment, the patients were administered nebivolol 5 mg once daily. After 12 weeks of nebivolol therapy, the biochemical and ultrasonographic examinations were repeated. Chest pain relief was detected in 38 patients after treatment (90%). Systolic and diastolic blood pressure and high sensitive CRP were significantly decreased after nebivolol therapy. Among brachial artery dilation variables that reflect endothelial function, basal resistive index (RI), post-flow mediated dilation RI, and post-nitrate mediated dilation RI were significantly decreased after therapy. Nebivolol is effective at improving endothelial function in patients with SCF. It controls chest pain, decreases CRP, and has favorable effects on brachial artery dilation variables in patients with coronary slow flow.

Effect of olmesartan medoxomil on cystatin C level, left ventricular hypertrophy and diastolic function.

Serum cystatin C concentration is an alternative measure of kidney function that is less affected by age, sex or muscle mass, and is a more sensitive indicator of early renal dysfunction than creatinine-based estimations of glomerular filtration rate. Cardiovascular sequela increases progressively with the increase in left ventricular mass. Our goal was to evaluate the effect of olmesartan medoxomil on cystatin C levels and left ventricular hypertrophy (LVH) in patients with hypertension. Forty-four newly diagnosed hypertensive patients (27 women and 17 men) were recruited in the study. Olmesartan medoxomil (20mg/day) was started and the patients were followed up for 6 months. Baseline echocardiographic findings (i.e. left ventricular mass index), serum creatinine, urine albumin/creatinine ratio (ACR) and serum cystatin C levels were compared with the levels of these variables measured at the end of 6-month follow-up period. After 6 months of treatment with olmesartan medoxomil, there was a significant reduction in systolic and diastolic blood pressure (p<0.001) and in urine ACR (p=0.04). Mean serum cystatin C levels decreased from 1.61+/-0.24 mg/l to 1.31+/-0.29 mg/l (p<0.001). Olmesartan medoxomil treatment also reduced left ventricular mass index (p<0.001) and LVH (p<0.001). Our findings indicate that olmesartan medoxomil decreases serum cystatin C levels, urine ACR and reduces LVH in patients with hypertension. To our knowledge, this study is the first to show that olmesartan medoxomil decreases serum cystatin C levels, indicating that in patients with essential hypertension it may counteract end organ damage.

Lifestyle and metabolic determinants of incident hypertension, with special reference to cigarette smoking: a longitudinal population-based study.

BACKGROUND: Lifestyle and metabolic determinants of incident hypertension in a population with a high prevalence of metabolic syndrome (MetS) need to be further assessed. METHODS: A representative sample of middle-aged and elderly Turkish adults was prospectively evaluated over a mean 7.4 years, after exclusion of prevalent hypertension and major renal dysfunction. RESULTS: In 2,427 men and women, aged 45.8 +/- 11.7 years, Kaplan-Meier analysis showed in combined genders mean time to incident hypertension to be 7.23 years in never, 7.78 years in current smokers (P < 0.001). Age and female sex were major determinants of subsequent hypertension after adjustment for physical activity grade, family income bracket, smoking status, usage of alcohol and of hormone replacement or birth control pill. Relative risk (RR) for incident hypertension of current vs. never smoking was reduced in women (P = 0.058) and both genders combined (P = 0.054). Former smokers uniformly exhibited significantly higher risk for the development of hypertension than both never (P = 0.054) and current (P < 0.001) smokers, whereby abdominally obese individuals were at increased risk. In further multivariable models, circulating C-reactive protein (CRP) and fasting insulin emerged as modest independent determinants and waist girth, modulated by current smoking, as a major determinant of subsequent hypertension. CONCLUSIONS: Age, female sex, and waist circumference are major and serum insulin and CRP modest determinants of incident hypertension in middle-aged Turkish adults in whom current cigarette smoking plays a protective role at borderline significance, largely by modulating waist girth. Former smokers with abdominal obesity are under higher risk of subsequent hypertension than current smokers.

Associations of alcohol consumption with blood pressure, lipoproteins, and subclinical inflammation among Turks.

Gender-related impact of alcohol consumption on blood pressure (BP), serum lipoprotein profile, and C-reactive protein (CRP) concentrations was evaluated prospectively. Alcohol drinking status was assessed as abstainers and categories of light, moderate, and heavy (daily >40 ml ethanol) intake. Mean age of the 3,443 men and women who were followed up for a mean of 7.4 years was 47.6+/-12 years. In each multivariable linear or logistic regression analysis, alcohol drinking status was adjusted for age, sex, smoking status, and physical activity. Among men, drinking was significantly associated positively with low-density lipo protein (LDL) cholesterol, apolipoprotein (apo) B, systolic and diastolic BP, and with CRP in a log-linear manner exhibiting features of a threshold at heavy drinking. With respect to response of serum triglycerides to light-to-moderate drinking, whereas men exhibited a significant increase, women exhibited a decline (P<.05). Lower BPs (P<.03) and CRP levels (P=.032) were observed in female drinkers than abstainers and, as distinct from men, no increases in LDL cholesterol and apoB were noted. Heavy drinking tended to protect the sexes against the risk of developing low high-density lipoprotein cholesterol levels in prospective multi adjusted analyses. Sex modulates response of cardiometabolic risk variables to moderate alcohol consumption among Turks. Only women respond with lower triglycerides and CRP, whereas men show a log-linear positive association of drinking categories with BP, LDL cholesterol, apoB, and CRP.