The Role of Osteoprotegerin as a Cardioprotective Versus Reactive Inflammatory Marker: the Chicken or the Egg Paradox

Cardiovascular disease is one of the most frequent causes of mortality and morbidity worldwide. Several variables have been identified as risk factors for cardiovascular disease. Recently, the role of receptor activator of nuclear factor kappa B, receptor activator of nuclear factor kappa B ligand, and the osteoprotegerin system has been recognized as more important in the pathogenesis of cardiovascular disease. Besides their roles in the regulation of bone resorption, these molecules have been reported to be associated with the pathophysiology of cardiovascular disease. There are conflicting data regarding the impact of osteoprotegerin, a glycoprotein with a regulatory role in the cardiovascular system. The aim of this review is to discuss the current knowledge and the role of osteoprotegerin in cardiovascular disease.

Phrenic neuropathy in diabetic and prediabetic patients without neuromuscular complaint.

Neuropathy, one of the major reasons of morbidity in diabetes mellitus (DM), is associated with prediabetic conditions as well as DM. The present study aims to compare phrenic and peripheral nerves in prediabetic, diabetic patients and healthy controls. A total of 37 diabetic, 40 prediabetic patients and 18 healthy controls were enrolled in the study. All subjects underwent conventional sensory and motor nerve conduction studies. Bilateral phrenic and peripheric nerve conduction studies were performed. In both right and left phrenic nerves, the amplitudes were lower in prediabetic and diabetic patients than control subjects, respectively (p: 0.005 and p: 0.001). Both of the phrenic nerve conductions were altered similarly. The results of our study demonstrate that phrenic nerves are affected like peripheric nerves in prediabetic and diabetic patients. We suggest reminding phrenic neuropathy in newly onset respiratory failure in diabetic and prediabetic patients.

An evaluation of glucose tolerance in essential hypertension.

PURPOSE: This study aimed to determine the impaired glucose tolerance and diabetes prevalence in patients with essential hypertension (HT) and to compare the developed microvascular complications of these groups. MATERIALS AND METHODS: An oral glucose tolerance test (OGTT) was performed on 338 essential hypertensive cases and glucose tolerances were classified according to ADA-2002 criteria. RESULTS: Of the 338 cases, 32 people had diabetes (DM, 9.46%), 78 people had glucose intolerance (IGT, 23.1%), and 228 people had only hypertension but not IGT and DM (67.4%). Both the mean ages of the DM group (56.9 +/- 6.7 years, p = 0.002) and IGT group (56.3 +/- 8.4 years, p = 0.003) were older than the mean age of the control group (51.1 +/- 6.4 years). The risk of IGT development was found to be four times greater in male cases than female cases when compared to the control group (p = 0.004, add ratio = 4.194). There were no significant differences in the body mass indexes (BMI's), hypertension durations, and microvascular complications between the groups. CONCLUSION: In conclusion, the risk of IGT and DM development in hypertensive cases increases with aging and longer hypertension duration. The risk of IGT development in hypertensive cases is four times more in males.

Silent myocardial ischemia in middle-aged asymptomatic patients with type 2 diabetes in Turkish population.

The authors investigated silent myocardial ischemia in unselected consecutive middle-aged asymptomatic patients with type 2 diabetes without any evidence of coronary heart disease documented by treadmill exercise test. Ninety asymptomatic patients with type 2 diabetes (48 men; mean age: 49 +/-6 years) were included in the study. Mean duration of diabetes in the study group was 4 +/-4.2 years (range 1 to 21 years); 38% of the study population, diabetes duration was only 1 year). All patients were subjected to treadmill exercise test with Bruce protocol. A positive test was noted in 4 of 90 (4%) study patients. Two male patients (4%) and 2 (4%) women patients developed exercise-induced ST-segment depression, but none had concomitant chest pain. Diabetics with silent myocardial ischemia were older (55 +/-3 years vs 49 +/-6 years, p = 0.04) than those without silent myocardial ischemia. Also, diabetics with silent myocardial ischemia had higher fibrinogen level (372 +/-51 vs 307 +/-71 mg/dL, p = 0.04) than diabetics without silent myocardial ischemia. In treadmill exercise test, diabetics with silent myocardial ischemia had lower total exercise time and peak workload (375 +/-30 vs 474 +/-115 seconds, p = 0.04; 7.3 +/-0.5 vs 8.9 +/-1.9, p = 0.04, respectively) than without silent myocardial ischemia. Insulin resistance is associated with a variety of atherosclerosis risk factors. Exercise test findings show increased cardiac sympathetic activity and parasympathetic withdrawal in increased insulin resistance.

Circulating leptin and osteoprotegerin levels affect insulin resistance in healthy premenopausal obese women.

We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women.

Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism.

INTRODUCTION: We assessed the alterations in regional cerebral blood flow (rCBF) in patients with primary hyperparathyroidism (PHP) before parathyroidectomy by semiquantitative analysis of brain single photon emission computed tomography (SPECT) images. METHODS: Included in this prospective study were 14 patients (mean age 47.6 +/- 10.4 years; 3 male, 11 female) and 10 control subjects (mean age 36.0 +/- 8.5 years, 6 male, 4 female) were SPECT imaging was performed using a dual-headed gamma camera 60-90 min after intravenous administration of 925 MBq Tc-99m HMPAO. The corticocerebellar rCBF ratios were calculated from 52 brain areas and reference lower values (RLVs) were calculated from the rCBF ratios of control subjects. The regional ratios that were below the corresponding RLV were considered abnormal (hypoperfused). RESULTS: Hypoperfusion was shown in 171 out of 728 regions (23%) and there was a significant correlation between serum calcium, PTH levels and the sum of hypoperfused regions in the patient group (R = 0.75 and P = 0.001, and R = 0.75, P = 0.001, respectively). Significantly reduced rCBF were found in the following cortical regions: bilateral cingulate cortex, superior and inferior frontal cortex, anterior temporal cortex, precentral gyrus, postcentral gyrus and parietal cortex, and right posterior temporal cortex. CONCLUSION: Our results indicate that alterations in rCBF in patients with PHP can be demonstrated with brain SPECT. The correlation between serum calcium, PTH levels and the sum of hypoperfused regions indicates that there may be a strong relationship between rCBF abnormalities and increased levels of serum calcium and PTH. In addition, the degree of rCBF abnormalities could be determined by brain SPECT in PHP patients with or without psychiatric symptoms.

Sympathetic skin response and RR interval variation in patients with cardiac syndrome X.

Sympathetic skin response (SSR) and R-R interval variation (RRIV) are noninvasive electrophysiological tests used in the assessment of sympathetic and parasympathetic nervous system function, respectively. Cardiac syndrome X (CSX) is usually diagnosed in the presence of typical angina pectoris, a positive response to exercise testing, and normal-appearing coronary angiograms without spasm induced by hyperventilation or ergonovine. Alterations of autonomic nervous system control of cardiac function have been described in CSX. The aim of the study was to investigate autonomic nervous system function in patients with CSX. Nine patients with CSX (2 men, 7 women) and healthy controls (11 men, 19 women) were included in the study. SSRs were recorded from palm of hands by stimulation of the median nerve. RRIV recordings were taken from precordium during both rest position (R%) and deep inspiration of 6 times per minute (D%). In addition D% - R% and D%/R% values were calculated. SSR amplitude of CSX was lower than in controls (3.64 +/-4.78 vs 6.36 +/-3.4 mV, p = 0.017). There was no difference between groups for SSR latency values (CSX: 1,366 +/-99; controls: 1,383 +/-85 msec). Also, R% (CSX: 13.04 +/-6.3; controls: 12.92 +/-3.91) and D% (CSX: 16.63 +/-8.88; controls: 21.43 +/-7.3) values were similar in the 2 groups. However, D% - R% (CSX: 3.59 +/-10.11; controls: 8.51 +/-7.01) and D%/R% (CSX: 1.45 +/-0.93; controls: 1.78 +/-0.69) values were slightly lower in patients with CSX but were not statistically significant. A linear correlation was found between SSR amplitude and D%/R% (r = 0.336, p = 0.036). The authors conclude that, among patients with CSX, there are alterations of autonomic nervous control of skin as well as of other organs (ie, heart). SSR and RRIV testing can be done easily in the neurophysiology laboratory to assess the sympathetic and parasympathetic system, respectively.

The relationship between insulin resistance assessed by HOMA-IR and serum osteoprotegerin levels in obesity.

AIM: We investigated the relationship between insulin resistance and serum osteoprotegerin (OPG) levels in healthy obese subjects and healthy lean controls. METHODS: Fifty obese subjects (age: 31+/-8 years) and 24 lean controls (age: 30+/-7 years) were included in the study. We used the homeostasis model assessment for insulin resistance (HOMA-IR) index as the index of insulin resistance. OPG levels were measured with the commercial ELISA kit. Obese subjects were studied in three groups: Group I (n = 25) HOMA-IR index < 2.24, Group II (n = 13) index 2.24-3.59, Group III (n = 12) index > 3.59. Group IV (n = 24) was the lean controls with HOMA-IR index < 2.24. RESULTS: Obese subjects with increased insulin resistance (Group III) had lower OPG values than other groups (11.88+/-7.43 pg/ml, 16.39+/-6.39 pg/ml, 17.37+/-9.61 pg/ml, and 18.1+/-6.65 pg/ml, respectively; Group I versus Group III p = 0.036; Group III versus Group IV p = 0.012). We also found significant inverse correlations between OPGc (corrected for BMI) and fasting glucose (r = -0.325, p = 0.005), fasting insulin (r = -0.404, p = 0.0001) as well as HOMA-IR (r = -0.428, p = 0.0001). Increased fibrinogen level was found in Group III than Group IV (9.32+/-1.97 micromol/l versus 7.47+/-1.65 micromol/l, respectively; p = 0.005). In conclusion, insulin resistance in obesity is associated with decreased serum OPG levels and increased fibrinogen levels. The relationship between serum OPG levels and HOMA-IR may provide an insight into vascular endothelial dysfunction in obesity.

Factors related to exercise capacity in asymptomatic middle-aged type 2 diabetic patients.

AIM: We aimed to look at the relationship between exercise capacity and metabolic variables in unselected consecutive asymptomatic middle-aged type 2 diabetic patients as a potential marker for undiagnosed coronary heart disease. METHOD: Ninety patients (49 +/- 6 years) were included in the study. All patients performed a treadmill exercise test using the Bruce protocol. According to achieved EC, patients were separated into three groups; Group I (n, 24) 8 > metabolic equivalents (METs) > or = 5, Group II (n, 54) 11 > METs > or = 8 and Group III (n, 12) METs > or = 11. RESULTS: Patients in group I are more likely to be of female gender and to have a family history of coronary heart disease (CHD) than in group III (P = 0.015, P = 0.009, respectively). When compared to group III, patients in group I had higher fasting insulin and fibrinogen levels (P = 0.049 and P = 0.01, respectively). Homeostasis model assessment for insulin resistance (HOMA-IR) index (P = 0.03) was also higher in group I than in group III. We found a significant negative correlation between achieved exercise capacity and age (r = -0.204, P = 0.048), fasting insulin (r = -0.209, P = 0.048), HOMA-IR (r = -0.204, P = 0.048) as well as fibrinogen (r = -0.301, P = 0.007). CONCLUSION: Reduced exercise capacity was associated with increased insulin resistance as assessed by HOMA-IR index in asymptomatic middle-aged type 2 diabetic patients.

Relationships existing between the serum cytokine levels and bone mineral density in women in the premenopausal period affected by Graves' disease with subclinical hyperthyroidism.

We examined the relationships existing between serum cytokine levels and bone mineral density (BMD) in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism. The study population consisted of 21 women with untreated hyperthyroid Graves' disease (group H) (age, 36 +/- 2 years), eight women with untreated subclinical hyperthyroid status (group SH) (age, 33 +/- 5 years) and 10 healthy women (group N) (age, 35 +/- 3 years). The following measurements were made in all patients: free T4 (fT4), free T3 (fT3), thyroid stimulating hormone (TSH), TSH receptor antibody (TRab), anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), interleukin-2 receptor (IL-2r), interleukin-4 (IL-4), interleukin-8 (IL-8) and interleukin-13 (IL-13). IL-2r and IL-8 levels significantly increased in group H compared with group SH (p < 0.01 and p = 0.05, respectively) and group N (p < 0.001 and p = 0.02, respectively). IL-4 and IL-13 levels tended to be lower in groups H and SH compared with group N, although this difference did not reach statistical significance. Bone mineral density was significantly reduced in only two areas of the femur in group H compared with group N. There was no difference in BMD between groups SH and N. There was no correlation between thyroid hormones, serum cytokine levels and BMD in either group. In conclusion, these results suggest that there were no relationships existing between the serum level of these cytokines and BMD in women of premenopausal age affected by Graves' disease with subclinical hyperthyroidism.

Increased P wave dispersion: a new finding in patients with syndrome X.

The present clinical study was undertaken in patients with syndrome X, namely angina with normal coronary arteries, to investigate the presence of increased P wave dispersion by comparing patients with coronary artery disease (CAD) and healthy control subjects. Three groups were studied - group A, 21 patients (48 6 years) with syndrome X; group B, 16 patients (56 9 years) with CAD; and group C, 16 healthy subjects (49 8 years). Patients with CAD were older than those in groups A and C (P=0.005 and P=0.035, respectively). All groups demonstrated similar PQ, QRS and RR intervals. Group B had a lower minimum P wave duration than group C (P=0.05). P wave dispersion in group A was found to be higher than that in groups B and C (P=0.018 and P=0.0001, respectively). Patients with syndrome X demonstrated increased P wave dispersion compared to patients with CAD and healthy subjects. High sympathetic tone or autonomic imbalance observed in patients with syndrome X may affect intra-atrial and interatrial conduction times, and leave them prone to develop atrial arrhythmias.