Köksal Ceyhan

Metabolic syndrome: major impact on coronary risk in a population with low cholesterol levels—a prospective and cross-sectional evaluation

UNLABELLED The prevalence and the excess coronary heart disease (CHD) risk of the metabolic syndrome (MS) and its components were investigated in the Turkish Adult Risk Factor Study in both a prospective and a cross-sectional manner. In a population sample, representative of Turkish adults who have low levels of high- and low-density lipoprotein-cholesterol (HDL-C and LDL-C), MS was identified in conformity with the definition used in the recent NCEP guidelines. Prospective analysis was based on 2398 men and women (mean age at baseline 49.1+/-13 years) who had a baseline examination in 1997/98 and were followed-up for a mean of 3 years. CHD was diagnosed based on clinical findings and Minnesota coding of resting electrocardiograms. Fatal and nonfatal CHD developed in 126 subjects. 27% of men and 38.6% of women were found to have MS at baseline examination. When adjusted for age, MS was an independent predictor of subsequent overall fatal and nonfatal CHD in both genders, displaying an RR of 1.71. At the final cross-sectional evaluation, coronary risk associated with MS in men was primarily accounted for by standard MS components (largely inherent in glucose intolerance, hypertension and in a surrogate of small, dense LDL particles), in addition to a minor independent contribution by C-reactive protein (CRP). In women with MS, a substantial residual coronary risk remained after controlling for five components, which was partly accounted for by levels of LDL-C and CRP. It was estimated that MS was the culprit in just over half the cases of CHD in Turkey. CONCLUSION MS was the major determinant of CHD risk in a population having generally low levels of HDL-C and LDL-C in middle-aged and elderly adults, extending to three out of every eight adults, and imposing an overall excess CHD risk of approximately 70%. In contrast to men, a substantial residual coronary risk is retained in Turkish women after controlling for five MS components.

Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders

AIMS Apolipoprotein C-III (apoC-III) has been recognized as a useful marker of triglyceride-rich lipoproteins (TRLs) metabolism and proposed as an indicator of prognosis for coronary risk in healthy subjects. We studied cross-sectionally in a population having low cholesterol levels, but a high prevalence of the metabolic syndrome, whether serum levels of total apoC-III or its sub-fractions were independent markers of prevalent coronary heart disease (CHD) or were related to variables reflecting the metabolic syndrome. METHODS AND RESULTS In 857 unselected participants of the representative population sample of the Turkish Adult Risk Factor Survey in 2001, apoC-III as well as other risk variables were evaluated, and CHD was diagnosed based on clinical findings and Minnesota coding of resting electrocardiograms. The sample consisted of men and women, aged 33-82 years, having a mean waist circumference of 89.4 and 92.9 cm, respectively, 42% of whom had the metabolic syndrome identified by criteria of the ATP III. ApoC-III values were measured by turbidimetric immunoassay. Mean concentrations for non-high-density lipoprotein (nonHDL) apoC-III in men and women were 6.4 and 6.2 mg/dl, respectively, and for apoC-III in HDL were 6.2 and 6.3 mg/dl, respectively. NonHDL apoC-III was similar to, and apoC-III in HDL was higher than that in Western populations. Both fractions of apoC-III were significantly correlated with lipids, lipoproteins, apoB, anthropometric measures, and blood pressures in both genders. Correlations for both were high with serum triglycerides (r(s)=around 0.70) and apoB (r(p)=around 0.37). Total apoC-III as well as both fractions were significantly correlated in women also with levels of inflammatory risk markers: strongly (r=0.40-0.45, P<0.001) with complement C3, and weakly (r(s)=around 0.20, P<0.001) with C-reactive protein. A cutoff of >7.0 mg/dl as opposed to lower levels of nonHDL apoC-III indicated the presence of hypertriglyceridemic hyperapo B with an age-adjusted odds ratio (OR) of 13.8; it indicated the presence of metabolic syndrome with 4.66-fold likelihood. Total apoC-III and nonHDL apoC-III proved to be significantly (P-trend <0.05 and 0.002) and strongly associated with prevalent CHD in men even after adjustment for age, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C): OR gradients across upper and lower quartiles were 3.88-fold (CI: 1.3; 11.4) and 8.8-fold (CI: 2.6; 29.8), respectively. CONCLUSIONS In a population among whom the metabolic syndrome prevails, total- and nonHDL apoC-III are each a determinant in both genders of the metabolic syndrome and of hypertriglyceridemic hyperapo B. Each is a powerful significant marker of prevalent CHD in men independent of LDL- and HDL-C levels. In women, despite being correlated with inflammatory risk markers, the significant association of elevated levels of apoC-III with CHD did not prove to be independent of age.

Increased aortic pulse wave velocity in obese children.

OBJECTIVES Obesity may start in childhood and obese children are more likely to grow up to be obese adults. Atherosclerosis is one of the most important complications of obesity. Pulse wave velocity (PWV), a noninvasive measure of arterial stiffness, is accepted to be an indicator of subclinical atherosclerosis. The aim of the study was to determine PWV in obese children. STUDY DESIGN The study included 30 obese (12 boys, 18 girls; mean age 13 ± 2 years) and 30 lean children (13 boys, 17 girls; mean age 12.5 ± 1.7 years). Weight and height were measured and obesity was defined as body mass index (BMI) of greater than the 95th percentile for age. All the subjects underwent echocardiographic evaluation and blood samples were obtained. Pulse-wave velocity was calculated using the following equation: PWV (m/sec) = height-based aortic length (cm)/(100xtransit time [sec]). The latter was measured as the difference in the time of onset of two flows at the diaphragm and the aortic valve. RESULTS Obese subjects had significantly higher blood pressure levels compared to the control group (p<0.001). The two groups were similar with respect to fasting glucose, hemoglobin, serum creatinine, and lipid levels. Among echocardiographic parameters, left ventricular end-diastolic dimension, interventricular septum thickness, posterior wall thickness, left ventricular mass index, left atrium dimension, and aortic root dimension were significantly increased in obese subjects compared to controls (p<0.01). Obese children had significantly higher PWV values than the controls (4.0 ± 0.8 vs. 3.3 ± 0.7 m/sec, p<0.001). A positive significant correlation was found between PWV and BMI (r=0.391, p=0.002). CONCLUSION Our findings show that aortic PWV is increased in obese children, suggesting that obesity may cause subclinical atherosclerosis even at early ages.

Cardiotrophin-1 plasma levels are increased in patients with diastolic heart failure

Summary Background Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in various cardiovascular diseases, including chronic heart failure. The aim of the study was to determine if plasma CT-1 is associated with diastolic heart failure (DHF) and to investigate the relationship between CT-1 and echocardiographic parameters. Material/Methods Fifty-seven consecutive patients (mean age 57±8 years, 24 males) diagnosed with DHF in our clinic and 33 controls (mean age 55±7 years, 12 males) were included in the study. All study participants underwent echocardiographic evaluation and blood samples were obtained. Results CT-1 and NT-proBNP values were significantly higher in DHF subjects than in controls (11.30 [8.09–16.51] vs. 17.5 [8.95–28.74] fmol/mL, P=0.017 and 64 [27.5–95] vs. 82 [55.5–241] pg/mL, P=0.009, respectively). The mitral peak velocity of early diastolic filling (E), mean ratio of E to early diastolic mitral annular velocity (E/Em), and the pulmonary capillary wedge pressure (PCWP) estimated from E/Em measurements were all significantly higher in the patient group (62.27±14.69 vs. 75.67±18.85 cm/sec, 6.40±1.48 vs. 10.30±3.48, and 10 [9–11]vs. 14[12–16] mmHg, P≤0.001 for all). Lateral and septal Em were significantly lower in the patient group (10.69±1.87 vs. 8.69±2.00 cm/sec and 8.91±1.22 vs. 6.65±1.58 cm/sec, P<0.001 for both). CT-1 positively correlated with NT-proBNP (P=0.001, r=0.349), mean E/Em (P=0.003, r=0.307), and estimated mean PCWP (P=0.001, r=0.308). Conclusions CT-1 is elevated in patients with DHF and is associated with NT-proBNP and estimated left ventricular filling pressures.

Fasting insulin levels independently associated with coronary heart disease in non-diabetic Turkish men and women.

BACKGROUND Levels of plasma insulin have been recognized as a weak risk indicator for coronary or cardiovascular risk in the general population with ethnic background and gender modifying this relationship. We assessed whether insulin concentrations are associated with or would serve as a marker of prevalent coronary heart disease risk in a cross-sectional study of a population having low cholesterol levels (just under 5 mmol/l) but higher prevalence of components of the metabolic syndrome. METHODS In 688 participants of the Turkish Adult Risk Factor Survey in 2001, plasma insulin values as well as other risk variables were evaluated, and coronary heart disease was diagnosed based on clinical findings and Minnesota coding of resting electrocardiograms. Nearly equal numbers of men and women (>30 years of age) constituted the population sample from the two largest regions of Turkey. Concentrations of insulin were determined by the chemiluminescent immunometric method. RESULTS Geometric mean value was 50 pmol/l (interquartile range 37-68 pmol/l), without revealing a significant difference in genders. Fasting insulin was correlated in both genders with many variables, notably those involving central obesity, triglycerides, blood pressure, physical inactivity and, inversely, with high-density lipoprotein (HDL)-cholesterol. In a regression model, waist circumference and body mass index were strongly associated with log insulin, after controlling for age and presence of coronary heart disease. The age- and obesity-adjusted odds ratio for coronary heart disease in the highest as opposed to the lowest quartile was 2-fold in both genders (P<0.05). Even after adjustment for dyslipidemia, blood pressure, glucose intolerance, physical activity and smoking status, an over 2-fold increased coronary heart disease risk still persisted with regard to hyperinsulinemia (>or=10 mU/l, 69.5 pmol/l). When C-reactive protein which was correlated with fasting insulin only in women, was added to the model, the impact of hyperinsulinemia on coronary heart disease risk remained unchanged. CONCLUSION Hyperinsulinemia (i) may provide information on the coronary heart disease likelihood over and above that provided by the other risk factors, including HDL-cholesterol, and (ii) may contribute, within the frame of insulin resistance, to the coronary heart disease risk independently of the classical risk factors.

Relation between fragmented QRS and collateral circulation in patients with chronic total occlusion without prior myocardial infarction.

OBJECTIVE It has been shown that the fragmented QRS (fQRS) on electrocardiogram (ECG) signifies regional myocardial scar in patients with non-Q-wave myocardial infarction (MI). We hypothesized that presence of fQRS on ECG may be related with poorly-grown collateral coronary circulation (CCC) in patients with chronic total coronary occlusion (CTO) without prior MI. METHODS This retrospective observational study is included 56 patients (mean age 61.73±7.96 years; 67.9% men) with CTO in one of the major coronary arteries. Collateral circulation was graded according to Rentrops classification. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous ECG leads corresponding to a major coronary artery territory. Patients with pathological Q-wave or history of MI, typical bundle brunch blocks (BBB) and incomplete right BBB were excluded from study. Statistical analysis was performed using Chi-square test, Students t-test and logistic regression analysis. RESULTS Fifteen patients had Rentrop grade 1, 15 patients had grade 2 and 26 patients had grade 3 CCC. Five (19%) of the patients who have grade 3 CCC, seven (47%) of the patients who had grade 2 CCC, ten (67%) of the patients who had grade 1 CCC had fQRS (p=0.002). Logistic regression analysis showed high predictive value of the presence of fQRS for Rentrop 1 CCC (OR=8.4, 95% CI 1.97-35.7; p=0.004). CONCLUSION Results of our study may implicate the presence of fQRS on electrocardiogram as a predictor of a poorly grown CCC in patients with chronic total occlusion without prior MI.

Mildly Decreased Glomerular Filtration Rate Is Associated With Poor Coronary Collateral Circulation in Patients With Coronary Artery Disease

The aim of this study was to evaluate the association between mildly decreased glomerular filtration rate (GFR) and coronary collateral circulation (CCC).

Fragmented QRS Complexes Are Associated with Increased Left Ventricular Mass in Patients with Essential Hypertension

Left ventricular hypertrophy (LVH) is an independent predictor of poor prognosis in patients with hypertension. In hypertensive hypertrophy, the pathophysiological mechanism is the accumulation of collagen in the myocardium. Fragmented QRS (fQRS) complexes are associated with myocardial fibrosis.

Coronary Ectasia Is Associated with Impaired Left Ventricular Myocardial Performance in Patients without Significant Coronary Artery Stenosis

Objectives: To determine both ventricular functions and tissue Doppler echocardiography (TDE)-derived myocardial performance index (MPI) in patients with coronary artery ectasia (CAE). Subjects and Methods: Twenty-five patients with CAE (13 men; mean age 57 ± 9 years) and 25 age- and sex-matched controls without CAE (8 men; mean age 54 ± 10 years) were enrolled in the study. Left and right ventricular functions were detected using conventional echocardiography and TDE. Results: Left ventricle-lateral wall (0.61 ± 0.17; 0.50 ± 0.10, p = 0.02), interventricular septum (0.66 ± 0.17; 0.52 ± 0.10, p = 0.007) and mean MPI (0.63 ± 0.15; 0.51 ± 0.09, p = 0.004) were increased in the CAE group compared to the control group. Right ventricular MPI was similar in both the CAE and control groups (0.58 ± 0.18; 0.52 ± 0.19, p > 0.05). Conclusion: The findings show that left ventricular MPI is different in CAE patients without obstructive coronary artery disease compared to the normal control group. Also in these patients, right ventricular MPI was similar to the control group.

Relationship between red cell distribution width and echocardiographic parameters in patients with diastolic heart failure

Red cell distribution width (RDW) was found to be a prognostic marker in heart failure patients. The aim of the study was to investigate the relationship between RDW and echocardiographic parameters in diastolic heart failure (DHF). Seventy‐one consecutive DHF patients (26 men) and 50 controls (21 men) were included in the study. All of the study population underwent echocardiographic evaluation, and blood samples were obtained. RDW and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) values were significantly higher, whereas there was an increasing trend for high‐sensitivity C‐reactive protein levels in DHF patients than those in controls (p < 0.001, p < 0.001, and p = 0.064, respectively). All of the echocardiographic parameters evaluating diastolic function were more deteriorated in the DHF group. Patients who had an RDW value greater than the cutoff point also had higher NT‐proBNP levels, an elevated ratio of mitral peak velocity of early diastolic filling to early diastolic mitral annular velocity, and increased estimated pulmonary capillary wedge pressures by tissue Doppler parameters, but lower creatinine clearance (p < 0.05 for all). According to the cutoff values calculated using receiver operating characteristic analysis, RDW > 13.6% and NT‐proBNP > 125 pg/mL have high diagnostic accuracy for predicting DHF. RDW values were increased in the DHF population. Our results suggest that the high RDW levels in patients with DHF may be related to increased neurohormonal activity, impaired renal functions, and elevated filling pressure, but not to increased inflammation.