Hasan Kutsi Kabul

Early myocardial functional alterations in patients with obstructive sleep apnea syndrome.

Background: There is limited information regarding myocardial alterations in patients with obstructive sleep apnea syndrome (OSAS) in the absence of pulmonary and cardiac comorbidity. In this study, we aimed to evaluate potential myocardial alterations of these patients and investigate the possible effects of OSAS‐related pathological variations on left and right ventricular functions. Methods: We studied 107 consecutive patients who were referred to our sleep laboratory for clinically suspected OSAS and 30 controls without any history or symptoms of sleep‐related disorders. Severity of OSAS was quantified by polysomnography. Patients with apnea–hypopnea index (AHI) < 5 were included in the OSAS (−) group (Group 1, n = 22). Subjects with AHI ≥ 5 were considered as OSAS and classified according to their AHI as mild‐to‐moderate (AHI ≥ 5 and AHI < 30) (Group 2, n = 45) and severe (AHI ≥ 30) OSAS groups (Group 3, n = 40). Conventional M‐mode, 2D, and Doppler mitral inflow parameters, tissue Doppler velocities, myocardial peak systolic strain, and strain rate values of various segments were measured and compared between groups. Results: Patients with OSAS displayed impairment of left ventricular diastolic function compared with controls. There were no significant differences between groups regarding parameters reflecting left ventricular systolic function. Myocardial strain analysis demonstrated significant decrement regarding apical right ventricular longitudinal peak systolic strain and strain rate values between groups in relation to the severity of OSAS. Conclusions: Patients with OSAS display a regional pattern of right ventricular dysfunction correlated with the severity of disease.

Relationship between increased systemic inflammation and impaired aortic elasticity in young patients with prehypertension.

AimThis study was designed to evaluate the possible relationship between vascular inflammatory status [namely, high-sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC)] and aortic elasticity parameters in patients with prehypertension. Materials and methodsThe study population consisted of 25 newly diagnosed prehypertensive individuals (18 men, mean age=34±6 years) and 25 healthy controls (16 men, mean age=33±6 years) eligible for this study. Aortic elasticity parameters were calculated from aortic diameters measured by echocardiography and blood pressures, simultaneously measured by sphygmomanometry. hs-CRP measurements were taken with latex-enhanced reagent using a Behring BN ProSpec analyzer. ResultsBaseline characteristics of patients with prehypertension and controls were homogeneous. Inflammatory markers were significantly higher in patients with prehypertension compared with those of controls [for WBC (×109/l): 11.46±0.77 (11.50) vs. 8.94±0.91 (9.20), P<0.001; for hs-CRP (&mgr;g/dl): 137.84±50.71 (130.00) vs. 78.30±35.20 (65.27), P<0.001]. There was a strong positive correlation between the mean aortic stiffness index and markers of inflammation (for WBC, r=0.857, P<0.001; for hs-CRP, r=0.858, P<0.001), whereas strong negative correlations were observed between aortic elasticity parameters and markers of inflammation (for aortic distensibility of WBC and hs-CRP, r=−0.862, P<0.001; r=−0.869, P<0.001, respectively, and for aortic strain of WBC and hs-CRP, r=−0.890, P<0.001; r=−0.906, P<0.001, respectively). ConclusionYoung prehypertensives have increased markers of inflammation, namely, hs-CRP and WBC, compared with controls. More importantly, impaired arterial stiffness is significantly associated with the markers of inflammation in patients with prehypertension.

Brain derived neurotrophic factor (BDNF) in cardiometabolic physiology and diseases

Important advances in our understanding of the relationships between adipose tissue derived peptides, namely adipokines, and their effects on cardiovascular functions have been achieved in recent years. Growing knowledge of adipokine biology is revealing the complexity of these proteins. Adipose tissue releases some other proteins called neurotrophins that are mainly active in central and peripheral nervous system. However, secretion and activity of these hormones are not only limited to neuronal cells and tissues, but they also take part in adipose tissue development, energy metabolism, glucose utilization, insulin sensitivity, inflammation, lipoprotein synthesis, and atherosclerosis. In this review, we describe the most recent advances in the functions of brain derived nerve growth factor (BDNF), a major type of neurotrophins, focusing primarily on cardiovascular and metabolic diseases.

Increased Serum Uric Acid Levels Are Correlated with Decreased Left Atrial Appendage Peak Flow Velocity in Patients with Atrial Fibrillation

Objective: We aimed to examine the relationship between serum uric acid levels and left atrial appendage (LAA) peak flow velocity, an indicator of the mechanical functions of the LAA, and atrial fibrillation (AF). Subjects and Methods: Transesophageal echocardiography was performed before cardioversion in 153 patients with AF. The patients were categorized into 2 groups based on their LAA blood flow velocity. Group 1 included 87 patients with a low LAA flow velocity (<35 cm/s), and group 2 comprised 66 patients with a normal LAA flow velocity (≥35 cm/s). The χ2 and Students t tests were used to compare categorical and quantitative data between the groups. Linear regression analyses were performed to demonstrate the independent association between serum uric acid levels and LAA peak flow velocity. Results: The LAA blood flow velocity was 24.62 ± 5.90 cm/s in group 1 and 49.28 ± 13.72 cm/s in group 2, respectively (p < 0.001). The serum uric acid levels were 6.88 ± 1.85 mg/dl in group 1 and 5.97 ± 1.51 mg/dl in group 2, and the difference was statistically significant (p = 0.001). There was a negative correlation between serum uric acid levels and LAA blood flow velocity (r = -0.216, p = 0.007). Multivariate regression analysis showed that serum uric acid levels, age and gender differences were significant predictors of the LAA peak flow velocity. Conclusions: High serum uric acid levels were associated with a low contractile function of the LAA and could provide additional prognostic information on future thromboembolic events in patients with AF.

The Effect of Age on Right Ventricular Diastolic Function in Healthy Subjects Undergoing Treadmill Exercise Test

There is an increasing interest for the value of right ventricle (RV) in predicting exercise tolerance and prognosis in cardiovascular disease. However, there is relatively few data evaluating the effect of age on RV diastolic filling velocities during rest or exercise in healthy subjects.

Ankle brachial index as a predictor of subclinical atherosclerosis in the elderly

We read with interest the article by Lim et al. showing the importance of screening of elderly subjects for the presence of subclinical atherosclerosis through multiple tools [1]. Peripheral arterial disease (PAD) is frequently accompanied by metabolic disturbances [2,3], and significant proportion of subjects with PAD die of cardiovascular causes [4,5]. The present letter was prepared to focus on the prevalence and features of PAD data presented by Lim et al., and to make comments on possible additive roles of ankle brachial index (ABI) measurement to detect subclinical atherosclerosis. First of all, although the past data from the Korean people seems insufficient, the present study is the first one that reported such a high prevalence (29.6%) of ABI detected PAD in an Asian country, even if the work was conducted on people over 65 years old. As possibly the best example, in a considerably large study on Korean subjects with diabetes, overall prevalence of PAD was found to be 3.2%, being less frequent in females [6], indicating a 6-fold lower prevalence of the disease which is clearly known to be more frequent in subjects with diabetes. Secondly, the authors excluded subjects with a high ABI which is increasingly encountered not only in the elderly but also in diabetes [7] that was present by 35% in the study population. Because a high ABI is equivalent to a low ABI in terms of predicting the low extremity occlusive disease [7] as well as mortality [8], an alternative approach in such studies may be inclusion of all subjects with a low or a high ABI by introducing an “abnormal ABI” classification. Third, while ABI≤0.9 successfully predicts presence of generalized atherosclerosis it is diagnostic for presence of PAD that is already an established cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis study, individuals with borderline (0.90– 0.99) and low-normal (1.0–1.09) ABI values were found to have significantly higher level of subclinical atherosclerosis and coronary heart disease prevalence both in men and in women [9]. The association between these ranges and overall death was also reported to be stronger than that of ABI values in the normal range [8]. Finally, the power of ABI testing in predicting cardiovascular risk is augmented when the lower ankle pressure is used for ABI calculation instead of the higher value, which may also be a sensitive approach to identify those individuals with subclinical atherosclerosis [10]. However, these latter two issues did not yet appear in the guidelines on PAD or cardiovascular disease prevention. It may be speculated that the weak associations between a low ABI and coronary stenosis or coronary artery calcium scores in the present study could have been improved by such alternative approaches; because, ABI is the easiest, cheapest, noninvasive and most widely available parameter among the tested tools and could help most clinicians to identify presence of subclinical atherosclerosis in their adult and elderly patients.

Relationship between Neutrophil-To-Lymphocyte Ratio and Electrocardiographic Ischemia Grade in STEMI

Background Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Changes in the QRS terminal portion have also been associated with adverse outcomes following STEMI. Objective To investigate the relationship between ECG ischemia grade and NLR in patients presenting with STEMI, in order to determine additional conventional risk factors for early risk stratification. Methods Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG performed on admission. White blood cells and subtypes were measured as part of the automated complete blood count (CBC) analysis. Patients were classified into two groups according to the ischemia grade presented on the admission ECG, as grade 2 ischemia (G2I) and grade 3 ischemia (G3I). Results Patients with G3I had significantly lower mean left ventricular ejection fraction than those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital mortality rate increased proportionally with the increase in ischemia grade (p = 0.036). There were significant differences in percentage of lymphocytes (p = 0.010) and percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis revealed that only NLR was the independent variable with a significant effect on ECG ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120–1.403, p < 0.001). Conclusion We found an association between G3I and elevated NLR in patients with STEMI. We believe that such an association might provide an additional prognostic value for risk stratification in patients with STEMI when combined with standardized risk scores.

Diagnosing PAD by calculating the ankle brachial index: Adherence to the guidelines

We read with interest the article by Stephens et al who examined how an ankle brachial index (ABI) measurement can be performed as part of the routine clinical practice in the primary care setting, starting from detecting the subjects to be screened and ending with appropriate referral of the patient for invasive testing or treatment. They enrolled a ‘‘sample’’ group to conduct ABI protocol and arterial waveform analysis and provided frequency data for peripheral arterial disease (PAD) as determined by ABI or other defined measures. There is no need to comment on the prevalence of a low ABI (# 0.9) in the present study, considering the very small sample size. However, several messages in the text may be misleading for readers because they are not in accordance with the current evidence and guideline recommendations. PAD is among the four major types of cardiovascular disease, being the least detected along with aortic atherosclerosis and/or aneurysm. Its value as a predictor of atherosclerotic diseases in other vascular beds outweighs its role as a diagnostic tool in detection of vascular occlusion in the lower extremities. Therefore, the concept of measuring ABI as a sustained clinical application seems to lead to widespread use of this technique in the near future. However, blood pressure readings and calculation of ABI in the routine should be uniform and should fully adhere to the guidelines. The details of ABI workup are frequently not given in articles, but a demonstrative one was presented by Grenon et al. In our clinic we further standardized the technique by implementing four steps: 1) to ensure the comfort of the arms, two metal plates 80 20 cm are placed on the head of the stretcher at an angle of 30 degrees; 2) all four extremities of the patient are wrapped with the same brand and model aneroid sphygmomanometers with Velcro cuffs; and 3) while the patient is supine, his or her ankles are supported upwardly by placing foam rubbers of 5 cm in height under the heels, preventing the cuffs from contact with the couch. This is also applied to the upper limbs at the elbows. In the fourth step, the readings are recorded, starting from the right arm, followed by the right ankle, left ankle and left arm. In research works, this cycle is repeated, and two values are recorded for each vessel. Considering the calculation of the ABI, the study by Stephens et al seems to have a major drawback. As seen in Table 2, the authors used only right-ankle pressure to calculate the ABI. This means that they recorded only the right ABI for each individual, indicating that left-ankle ABI was not taken into account in determining the final ABI. However, in the PARTNERS survey, which seems to be the model study referenced by the authors, right and left ABIs were determined separately by taking the highest of the pedal pulses in each ankle, and the lowest of the calculated right and left ABIs was accepted as the final ABI of the patient. We also applied this method in the last year to the Turkish national PAD survey which was also designed in a way that was similar to that of the PARTNERS study. Indeed, beyond solitary studies, the guideline recommended technique of ABI calculation is not in accordance with the one used in the study by Stephens et al. Both ACC/AHA 2005 practice guidelines for the management of patients with PAD and Inter-Society Consensus for the Management of PAD guideline (TASC II) were based on the same method of calculation. Moreover, 2011 ACCF/AHA focused update of the 2005 guideline and the first ESC-released guideline specific to PAD recommended continuing with the previously determined calculation method. Although some of these studies were referred to by the authors, a true definition of ABI calculation could not be made in their study. Application of the correct method is especially important when we consider that, by using this value, the clinicians diagnose PAD and not only the prognosis but also the management of the individual changes substantially after such a decision. Finally, besides improving physician awareness of PAD, increasing patient awareness of the condition and its management is essential to improve quality of life and decrease costs. However, the conclusion that the protocol for ABI screening increased patient awareness of risks and risk-factor modifications in the investigation by Stephens et al is subjective because the study does not seem to have included such a parameter and did not report measuring that at all.

Relationship between Pulmonary Artery Stiffness and Functional Capacity in Patients with Heart Failure with Reduced Ejection Fraction

Background and Objectives Functional capacity varies significantly among patients with heart failure with reduced ejection fraction (HFrEF), and it remains unclear why functional capacity is severely compromised in some patients with HFrEF while it is preserved in others. In this study, we aimed to evaluate the role of pulmonary artery stiffness (PAS) in the functional status of patients with HFrEF. Methods A total of 46 heart failure (HF) patients without overt pulmonary hypertension or right HF and 52 controls were enrolled in the study. PAS was assessed on parasternal short-axis view using pulsed-wave Doppler recording of pulmonary flow one centimeter distal to the pulmonic valve annulus at a speed of 100 mm/sec. PAS was calculated according to the following formula: the ratio of maximum flow velocity shift of pulmonary flow to pulmonary acceleration time. Results PAS was significantly increased in the HFrEF group compared to the control group (10.53±2.40 vs. 7.41±1.32, p<0.001). In sub-group analysis of patients with HFrEF, PAS was significantly associated with the functional class of the patients. HFrEF patients with poor New York Heart Association (NYHA) functional capacity had higher PAS compared those with good functional capacity. In multivariate regression analysis, NYHA class was independently correlated with PAS. Conclusion PAS is associated with functional status and should be taken into consideration as an underlying pathophysiological mechanism of dyspnea in patients with HFrEF.

Individual variations in ankle brachial index measurement among Turkish adults

Purpose Variability of ankle brachial index (ABI) measured by the same observer in the same individual on three different occasions was examined. Basic methods A single morning ABI was initially determined (measurement 1) with handheld Doppler device. One to four weeks apart, another morning (measurement 2) and afternoon (measurement 3) ABI was measured on the same day. Principal findings A total of 161 adults were enrolled. Mean ABI was similar among the three measurements. ABI differed more than ≥0.15 in 15 individuals between measurement 1 and 3, in 10 subjects between measurement 1 and 2, and in 12 individuals between measurement 2 and 3. Intra-group correlation coefficients of reproducibility of ABI were 0.808 for single measurements (coefficient of the values lacking association with each other), and 0.927 for average measurements (coefficient of the values that were associated with each other). Conclusions Although reproducibility of ABI values was found satisfactory, up to 12% of participants displayed more than 0.15 alternations between measurements, either on the same day or more than a week apart.