Murat Unlu

Neutrophils/Lymphocytes Ratio in Patients With Cardiac Syndrome X and Its Association With Carotid Intima–Media Thickness

Neutrophils and lymphocytes (N/L) ratio and carotid intima–media thickness (C-IMT) value have been studied as new predictors of cardiovascular risk. We aimed to investigate N/L ratio and C-IMT value in patients with cardiac syndrome X (CSX) and compare patients with coronary artery disease (CAD) and normal participants. A total of 288 participants were enrolled in the study. The N/L ratio and C-IMT value were compared among the 3 groups. There were no statistically significant differences in N/L levels between CSX and CAD groups. The N/L ratio was found significantly increased in patients with CSX and CAD, compared to the control group. Patients with CAD and CSX had significantly higher C-IMT value compared to control participants. Significant positive correlation was found between C-IMT value and plasma level of N/L ratio. The relationship among CSX and higher N/L ratio level and C-IMT suggests that endothelial dysfunction may contribute to the etiopathogenesis of the CSX.

Prevalence of testicular microlithiasis in an asymptomatic population

Testicular microlithiasis is a rare, usually asymptomatic, finding of the testes associated with various genetic anomalies and infertility. It is also widely believed that testicular microlithiasis is strongly associated with testicular tumor. The aim of this prospective study was to determine the true prevalence of testicular microlithiasis in an asymptomatic population by means of ultrasound screening. Healthy male volunteers (17–42 years old) were recruited from the annual Army Reserve Officer Training Corps training camp at Manisa, Turkey. A screening genitourinary history was obtained and a physical examination and screening scrotal ultrasound scan were performed. All men diagnosed with testicular microlithiasis underwent complete clinical evaluations, physical examinations and determination of tumor markers. Fifty-three men with testicular microlithiasis were identified from the 2179 ultrasound scans, giving a prevalence of testicular microlithiasis of 2.4% in this asymptomatic population. The age (mean±SD) of subjects with testicular microlithiasis was 23.9±4.2 years (range 20–31 years). Our results suggest that there is no significant association between TM and testicular cancer, although it is difficult to rule out such an association without further studies with a longer follow-up period.

Carotid intima-media thickness in patients with slow coronary flow and its association with neutrophil-to-lymphocyte ratio: a preliminary report.

Background: The slow coronary flow (SCF) is characterized by angiographically normal or near-normal coronary arteries with delayed progression of the contrast agent into distal vasculature. We aimed to investigate neutrophil-to-lymphocyte (N/L) ratio and the carotid intima-media thickness (CIMT) value in patients with SCF compared to patients with newly diagnosed coronary artery disease (CAD) and normal patients. Materials and Methods: We enrolled 60 consecutive patients with SCF, 68 patients with CAD, and 72 normal patients. The association between thrombolysis in myocardial infarction frame count, CIMT, and N/L ratio and other clinical and laboratory parameters were evaluated. Results: The N/L ratio was significantly higher not only in patients with SCF but also in patients with CAD, compared to those of controls. The N/L ratio was positively and moderately correlated with CIMT in the whole study population. Conclusions: The NL ratio is significantly associated with reduced coronary blood flow, and elevated N/L ratio might be an independent predictor for the presence of SCF.

Anatomic and hemodynamic evaluation of renal venous flow in varicocele formation using color Doppler sonography with emphasis on renal vein entrapment syndrome

Objective. To investigate the anatomic and hemodynamic properties of testicular venous drainage and its effects on varicocele formation and reflux using color Doppler ultrasound (US) with emphasis on renal vein entrapment syndrome. Material and methods. Upper abdominal and scrotal US examinations of 35 varicocele patients and 35 healthy male subjects were performed in the supine position during rest, during a Valsalva maneuver and in the erect position. The aortomesenteric angle and distance (AMA and AMD, respectively), peak mean velocities (PVs) and diameters of different segments of renal veins, testicular vein diameters and duration of flow inversion were measured. Results. In the varicocele group, the lateral segment of the left renal vein (LRV) had a larger diameter and slower PV, and the medial segment of the LRV had a smaller diameter and faster PV. The diameter of the dominant draining vein correlated with the PV of the medial and lateral segments of the LRV, whereas there was no correlation between the diameter of the dominant draining vein and the diameters of the right renal vein (RRV) and the lateral segment of the LRV or the PV of the RRV. The duration of flow inversion correlated with the diameter and PV of the medial segment of the LRV. No correlation between the diameters and PVs of the RRV and the lateral segment of the LRV was detected. Conclusions. The decreases in the AMA, AMD, diameter of the medial segment of the LRV and PV of the lateral segment of the LRV, and the increases in the PV of the medial segment of the LRV and the diameter of the lateral segment of the LRV in varicocele patients in all positions suggest the entrapment or impingement of the left renal vein between the aorta and the superior mesenteric artery. This has been defined as the “nutcracker phenomenon”, which is known to affect varicocele formation.

Other inflammatory markers should be kept in mind when assessing the mean platelet volume.

We read with a great interest the article ‘‘Increased mean platelet volume (MPV) and mean platelet volume/platelet count (MPV/P) ratio in Korean patients with deep vein thrombosis (DVT)’’ written by Han and coworkers [1]. They aimed to compare the MPV and MPV/P ratio between DVT and control subjects. They demonstrated that MPV was higher in DVT patients compared to controls. The DVT patients also had a higher MPV/P ratio compared to the control group. MPV was conversely correlated with the platelet count in DVT patients. They suggested that the MPV and MPV/P ratio may be considered meaningful laboratory markers for the risk of DVT. The study is successful in design and documentation. DVT is a common disease found worldwide. It presents symptoms ranging from asymptomatic to fatal pulmonary embolism. So, prevention and early diagnosis of DVT are very important. The presence of DVT was closely associated with increased platelet activation [2]. Blood stasis, vascular endothelial injury, and hypercoagulable conditions are well-known risk factors of DVT. It has also been related to obesity, smoking, previous surgical history, trauma, cancer, immobilization and another platelet dysfunctions [3]. In contrast to the present study, the authors demonstrated downregulation of platelet activation after long-term immobilization in the previous study [4]. For this reason, we think that because platelet function can affect various factors, further studies should consider these conditions. A complete blood count is a routine, easy, and cheap examination technique that gives information about the patient’s formed blood contents; the red and white cells, platelets, the counts and dimensions of subgroups of cells, and parameters like the distribution widths, mean platelet volume. MPV is one of the most widely used laboratory markers to be related to the platelet function based on the inflammatory condition [5,6]. MPV also indicates the function of platelet, which is central to processes that are involved in coronary heart disease pathophysiology and endothelial dysfunction [7,8]. Platelet parameters can be affected by coronary risk factors including age, obesity, smoking, diabetes mellitus, hypertension, hyperlipidemia metabolic syndrome [6]. Another study demonstrated that MPV can be predicted in patients with stroke [9]. Some other recent studies have presented that elevated MPV is linked with peripheral artery disease and stroke, all of which are related to atherosclerosis on the basis of inflammation [5]. Previous studies demonstrated an association between the long-term mortality after non-ST-segment elevation myocardial infarction and the peripheral blood platelet indices including the MPV, platelet count, and the MPV/P ratio [10]. It can also be affected by thyroid and rheumatic diseases [11,12], malignancy and medications such as anticoagulant therapy, statins. So, if the authors had mentioned these factors, it might be useful. MPV is as an important marker of inflammation. Previous study has shown that MPV showed significant differences in patients with hepatic diseases [13]. On the other hand, MPV value was higher in chronic obstructive pulmonary disease patients compare with those of the control group [14,15]. Therefore, if the authors gave information about hepatic function tests and respiratory condition, the results of the present study may be different and stronger. Additionally, it would be better if the authors defined how much time they specified on measuring MPV levels, because the delaying blood sampling can cause abnormal results in MPV measurements. Finally, MPV may be affected by many factors, the routine clinical usage of these parameters may not be reasonable yet. MPV itself alone without other overt inflammatory markers may not give information to clinicians about the chronic endothelial inflammatory condition of the patient at the first look. So, we think that it should be evaluated together with other inflammatory markers. We believe that these findings will guide further studies about MPV as a surrogate marker of endothelial dysfunction and inflammation in patients with DVT. We thank the authors for their contribution.

Hemostatic markers can be pivotal roles of risk factors for new-onset atrial fibrillation

We have read the recently published article entitled ‘‘Usefulness of the mean platelet volume (MPV) for predicting new-onset atrial fibrillation (AF) after isolated coronary artery bypass grafting (CABG)’ by Erdem and coworkers [1]. In that very well-designed and presented study, Erdem and coworkers tried to determine whether preoperative MPV is associated with the development of AF after CABG. They concluded that MPV was significantly higher in patients with postoperative AF than the control group. In addition, they found that MPV was an independent predictor of postoperative AF with multivariate analyses. Atrial fibrillation is the most common cardiac arrhythmia in clinical practice, expected to affect millions of people worlwide. AF is responsible for considerable morbidity and mortality, making identification of modifiable risk factors a priority. Postoperative AF usually complicates CABG. New-onset AF after CABG appears to increase shortand long-term mortality. Caucasians are at higher risk for AF after isolated CABG than are persons of other races. Race probably is a surrogate for unrecognized variables such as genetic disparities among racial/ ethnic groups [2]. In the previous large population-based study, higher serum phosphorus level and the related calcium-phosphorus product were found to be related to the increased risk of AF [3]. Proteinuria was also apparently linked to the AF [4]. On the other hand, elevated transaminase concentrations were associated with the increased risk of AF [5]. Elevated preoperative brain natriuretic peptide (BNP) levels and advanced age together are significant predictors for the development of postoperative AF in patients undergoing isolated CABG [6]. Clinical trials support evidence that the application of a multidrug prophylaxis can reduce postoperative AF to a low incidence [7]. Preoperative management, such as use of ß-blockers, avoidance of angiotensin-converting enzyme inhibitors, and shorter cardiopulmonary bypass and aortic clamp times can reduce incidence of new-onset AF [8]. Bisphosphonate use was associated with a significant increase in the risk of serious AF [9]. Another interesting study tried to examine whether or not exposure to non-steroidal anti-inflammatory drugs (NSAIDs) was a risk factor for AF. They found that recent NSAID use may predispose patients to AF [10]. Moreover, it was demonstrated that several hemostatic markers are associated with the incidence of AF independent of other cardiovascular risk factors [11]. Platelet abnormalities in AF may underline the etiology of a prothrombotic state in the condition. Increased MPV is a marker of abnormal platelet function and activation [12]. MPV is one of the most widely used laboratory markers related to the platelet function based on inflammatory conditions [13,14]. MPV also indicates the function of platelet, which is central to processes that are involved in coronary heart disease pathophysiology and endothelial dysfunction [15,16]. Platelet paremeters can be affected by coronary risk factors, including age, obesity, smoking, diabetes mellitus, hypertension, and hyperlipidemia metabolic syndrome [14]. Some other recent studies have presented that elevated MPV is linked with peripheral artery disease and stroke, all of which are related to atherosclerosis on the basis of inflammation [17]. It can also be affected by thyroid and rheumatic diseases [18,19], malignancy and medications such as anticoagulant therapy, statins. In a previous study, the authors had demonstrated that MPV showed significant differences in patients with hepatic diseases [20]. On the other hand, MPV value was higher in chronic obstructive pulmonary disease patients compared with those of the control group [21]. Finally, MPV may be affected by many factors, the routine clinical usage of these parameters may not be reasonable yet. MPV itself alone without other overt inflammatory markers may not give information to clinicians about the chronic endothelial inflammatory condition of the patient at the first look. So, we think that it should be evaluated together with other inflammatory markers. In conclusion, MPV is an essential risk factor for incident AF after CABG and more importantly MPV explains much of the increased AF risk associated with platelet activity in the current study. However, risk factors for incident AF after CABG are very complex and the pivotal roles of those risk factors deserve further large-scale prospective randomized clinical trials. Keywords

Inflammatory status as a major role of risk factor for atrial fibrillation

To the Editor, We have read with great enthusiasm the recently published article entitled ‘‘Elevated levels of red cell distribution width (RDW) is associated with non-valvular atrial fibrillation (AF)’’ by Gungor et al. [1]. In that very welldesigned and presented study Gungor et al. tried to determine the association between the RDW and non-valvular AF. They concluded that Elevated RDW level may be used as a risk marker for non-valvular AF. Atrial fibrillation, the most common cardiac arrhythmia in clinical practice, is expected to affecting millions of people in the worlwide [2]. AF is responsible for considerable morbidity and mortality, making identification of modifiable risk factors a priority. Some factors such as elevated transaminase concentrations are related to increased risk of AF [3]. On the other hand, proteinuria was also apparently linked to the AF [4]. Moreover it was demonstrated that several hemostatic markers are associated with the incidence of AF independently of other cardiovascular risk factors. In the previous large populationbased study, greater levels of serum phosphorus and the related calcium-phosphorus product were found to be associated with a increased risk of AF [5]. Bisphosphonate use was associated with a significant increase in the risk of serious AF in postmenopausal women. In another interesting study tried to examine whether or not exposure to non-steroidal anti-inflammatory drugs (NSAIDs) was a risk factor for AF. They found that recent NSAID use may predispose patients to AF [6]. Several routine haematology instruments can analyse erythrocyte volume, RDW is available in most clinical settings. RDW is a quantitative measure of anisocytosis, the variability in size of circulating erythrocytes. It is reported routinely as part of the full blood count and is elevated in several aberrations (e.g. iron deficiency, inflammation, nutritional status, transfusion history) [7]. Recently, a number of studies have been reported that the elevated RDW levels are associated with ethnicity, neurohumoral activation, renal dysfunction, thyroid disease, hepatic dysfunction nutritional deficiencies (i.e., iron, vitamin B12, and folic acid), bone marrow dysfunction, inflammatory diseases, chronic systemic inflammation and use of any medications [8]. RDW was measured at the time on during application of AF, rather than at the beginning of AF in current study [1]. So, the time gap between the RDW test and the beginning of AF may affect the results of the study. Additionally, it would be better if the authors defined how much time they specified on measuring RDW levels, because of the delaying blood sampling can cause abnormal results in RDW measurements [9]. RDW is a novel marker of inflammation. Previous study, the authors had shown that RDW showed significant differences in patients with hepatic diseases. On the other hand, RDW value was higher in chronic obstructive pulmonary disease patients compare with those of control group [10]. Therefore, if the authors gave information about hepatic function tests and respiratory condition, the results of the present study may be different and stronger. Finally, The ready availability of this parameter at no additional cost may encourage its wider use in clinical practice in the future. However, RDW may be affected by many factors, the routine clinical usage of these parameters may not be reasonable yet. RDW itself alone without other S. Balta (&) S. Demirkol Z. Arslan M. Unlu T. Celik Department of Cardiology, Gulhane Medical Academy, Gulhane School of Medicine, Tevfik Saglam Street, Etlik, 06018 Ankara, Turkey e-mail: drsevketb@gmail.com

The Relation Between Neutrophil-Lymphocyte Ratio and Endothelial Dysfunction.

We read the article ‘‘Neutrophil–Lymphocyte Ratio and Carotid– Intima Media Thickness in Patients With Behçet Disease Without Cardiovascular Involvement’’ by Ozturk et al with interest. They evaluated the neutrophil–lymphocyte ratio (NLR), carotid intima–media thickness (cIMT), and Behçet disease (BD) activity in patients without cardiovascular involvement. They reported a high NLR, a positive correlation between cIMT and NLR, and suggested that a high NLR is related to endothelial dysfunction and reflects BD activity. Behçet disease is associated with endothelial dysfunction and chronic inflammation. Endothelial dysfunction is an early step in atherogenesis and it can be assessed by markers such as cIMT and arterial stiffness. A complete blood count routinely measured using automated cell counters is an inexpensive and easy to interpret test. Compared with other markers of endothelial activity, blood parameters such as the NLR are practical and prognostically useful in many conditions. 4 However, in a previous study, Alkaabi et al evaluated the cause of thrombosis in BD. They reported that the values of factor VIII:C, von Willebrand factor antigen, antithrombin, and protein S most likely represent an acute-phase phenomenon and were significantly higher in the BD group. They hypothesized that active BD causes vasculitic endothelial perturbation with dysfunction, leading to an increased propensity for thrombosis. Ozuguz et al reported increased levels of mean high-sensitivity C-reactive protein, erythrocyte sedimentation rate, homocysteine, and asymmetric dimethylarginine (ADMA) in the BD group, especially in those with active disease. Flow-mediated dilatation (FMD) was significantly lower in patients with BD than in controls. The FMD correlated negatively with BD duration and serum ADMA levels; a positive correlation was also seen between serum ADMA levels and BD duration. They concluded that FMD in conjunction with markers of inflammation may evaluate endothelial dysfunction in BD. Ozturk et al showed higher cIMT and NLR levels in patients with BD compared to controls but some of the above-mentioned markers could have been considered and correlated the NLR. In conclusion, the relationship between NLR and other widely accepted markers in BD should be evaluated in largescale prospective randomized trials.

Mean platelet volume can be affected by many factors and should be assessed together with other inflammatory markers

We read with a great interest the article ‘‘Mean platelet volume (MPV) and abnormal left ventricle (LV) geometric patterns in patients with untreated essential hypertension’’, written by Zafer Elbasan and coworkers [1]. They aimed to investigate the relationship between MPV and abnormal LV geometric patterns in hypertensive patients. They demonstrated the highest MPV values were observed in the concentric hypertrophy (CH) group, MPV values were similar among the normal LV geometry (NG), concentric remodelling (CR) and eccentric hypertrophy (EH) groups, high sensitive C-reactive protein (hsCRP) value showed an increasing trend from NG group to CH group and MPV was independently associated with hsCRP and LV mass index (LVMI) besides age. The study is successful in design and documentation. We believe that these findings will guide further studies about MPV as a surrogate marker of endothelial dysfunction and inflammation in patients with untreated essential hypertension. We thank to the authors for their contribution. A complete blood count is an easy and cheap examination technique that provides information about the patient’s formed blood contents; the red and white cells, platelets, the counts and dimensions of subgroups of cells, and parameters like the distribution widths. MPV is the most commonly used method to measure the platelet size [2]. MPV is the indicator of platelet activation, which is central to processes that are involved in coronary heart disease pathophysiology and endothelial dysfunction [3, 4]. Platelet parameters can be affected by coronary risk factors including age, obesity, smoking, diabetes mellitus, hypertension, hyperlipidemia metabolic syndrome [5]. Another study demonstrated that MPV can be predicted in patients with stroke [6]. Some other recent studies have presented that elevated MPV is linked with peripheral artery disease and stroke, all of which are related to atherosclerosis on the basis of inflammation [2]. It can also be affected by thyroid and rheumatic diseases [7, 8], malignancy and medications such as anticoagulant therapy, statins. So, if the authors had mentioned these factors, it might be useful. Mean platelet volume is as an important marker of inflammation. In the previous study, the authors had shown that MPV showed significant differences in patients with hepatic diseases [9]. On the other hand, MPV value was higher in chronic obstructive pulmonary disease patients compared with those of the control group [10, 11]. Therefore, if the authors gave information about hepatic function tests and respiratory condition, the results of the present study may be better and stronger. Finally, MPV may be affected by many factors, the routine clinical usage of these parameters may not be reasonable yet. MPV itself alone without other overt inflammatory markers may not give information to clinicians about the chronic endothelial inflammatory condition of the patient at the first look. So, we think that it should be evaluated together with other inflammatory markers.

Ankle-Brachial Index and Cardiovascular Outcome.

We read the article ‘‘The Ankle-Brachial Index is Associated With Cardiovascular Complications After Noncardiac Surgery’’ by Carmo et al with interest. They evaluated the role of ankle–brachial index (ABI) as a predictor of cardiovascular (CV) complications in patients with and without an abnormal ABI submitted to noncardiac surgery. An ABI 0.9 indicated a >7-fold chance for the occurrence of the primary outcome. Patients with symptomatic and asymptomatic atherosclerosis or several risk factors have relatively high rates of CV events. Additionally, several studies demonstrated an independent positive association between asymptomatic peripheral artery disease (PAD) and CV events, including stroke, transient ischemic attack, myocardial infarction, and death among patients with previous stroke. Serena et al analyzed the adjusted predictive capacity of the ABI together with additional markers of atherothrombotic disease as predictors of CV events. In the ARTICO stroke population, symptomatic PAD and particularly the association of both symptomatic PAD and ABI 0.9 with internal carotid artery stenosis >50% were independently associated with a 3.72 and 4.39 times increased risk of new vascular events. The ABI is a relatively simple, easy, noninvasive, and inexpensive test, and it is >90% sensitive and specific compared with angiography, the gold standard. Although the ABI provides several benefits, it also has limitations. For example, 10% of the general population have a congenital absence of the dorsalis pedis or posterior tibial artery meaning that ABI would not be accurate. In conclusion, Carmo et al describe the ABI as a predictor of CV complications in patients with noncardiac surgery. This relationship needs to be evaluated in large-scale prospective randomized clinical trials.