Galina Shenkerman

Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men

OBJECTIVE To assess arterial stiffness in a cohort of hypogonadal males and to investigate the effect of testosterone replacement therapy on arterial properties in this specific group. DESIGN Eighteen male patients with untreated acquired hypogonadism due to either adult-onset idiopathic hypogonadotropic hypogonadism (n=9) or pituitary tumor (n=9) and 12 age-, sex, and weight-matched eugonadal healthy controls were recruited for the study. Arterial properties, plasma glucose, lipid profile, total, and bioavailable testosterone (BT) levels were measured in fasting state. In the hypogonadal subjects, the effect of transdermal testosterone replacement therapy on arterial properties was studied by repeat noninvasive measurements at baseline, as well as 48 h and 90 days following the initiation of treatment. METHODS Arterial stiffness was evaluated using applanation tonometry and pulse wave analysis by three different standard devices that assess various measures of arterial stiffness: pulse wave velocity (PWV), augmentation index (AIx), and large/small artery compliance (C1 and C2). RESULTS Age- and blood pressure-adjusted PWV was significantly higher in hypogonadal men (8.90+/-2.29 vs 6.78+/-1.16 m/s in the control group; P=0.025). Testosterone therapy increased BT level from 2.01+/-1.04 to 4.68+/-2.43 and 7.83+/-6.2 nmol/l after 48 h and 3 months respectively (P=0.001). PWV decreased from 8.9+/-2.29 to 8.24+/-1.39 and 8.25+/-1.82 m/s after 48 h and 3 months of treatment respectively (P=0.03). CONCLUSIONS Male hypogonadism is associated with increased PWV, which is rapidly but incompletely ameliorated by normalization of circulating testosterone levels.

Cardiovascular risk factors and arterial rigidity are similar in asymptomatic normocalcemic and hypercalcemic primary hyperparathyroidism.

OBJECTIVE It is still uncertain whether mild primary hyperparathyroidism (PHPT) carries the same risk for increased cardiovascular (CV) morbidity as the more severe symptomatic form. In recent years, the even more subtle normocalcemic (NC) variant is being increasingly recognized. We sought to compare the prevalence of CV risk factors in patients with NC- and hypercalcemic (HC)-PHPT, and to examine whether they differ on a battery of non-invasive vascular parameters. DESIGN/SUBJECTS/METHODS: A retrospective study of two cohorts of patients with PHPT in a referral center: 32 subjects with NC-PHPT and 81 subjects with HC-PHPT, compared for the presence of clinical and biochemical risk factors, and CV morbidity. Non-invasive parameters of arterial stiffness (augmentation index; pulse wave velocity; and vascular compliance indices, C1 and C2) were extracted from the data of gender- and age-matched subsets of these patients, and were related to those of a group of matched control subjects. RESULTS Despite a similar prevalence of hypertension (approximately 62%), hyperlipidemia (approximately 30%), and impaired glucose metabolism in both PHPT groups, CV or cerebrovascular disease was more common in the HC-PHPT group (24.7 vs 3.1%, P=0.007). Arterial stiffness parameters did not differ in the three groups, and were unrelated to serum calcium or parathyroid hormone concentration. CONCLUSIONS NC-PHPT and HC-PHPT subjects exhibit similar high rates of traditional CV risk factors, and have comparable indices of arterial stiffness. The lower clinical CV morbidity observed with NC-PHPT remains unexplained, and requires confirmation. Until then, the CV risk associated with NC-PHPT should not be underestimated.

Platelet counts and platelet activation markers in obese subjects.

Objective. In this work we studied the correlation between platelet count, platelet activation, and systemic inflammation in overweight, obese, and morbidly obese individuals. Methods and subjects. A total of 6319 individuals participated in the study. Complete blood counts, high sensitivity C-reactive protein (hs-CRP) serum levels, and body mass index (BMI) were measured during routine checkups. Platelet activation markers were studied among 30 obese (BMI = 41 ± 8 kg/m2) and 35 nonobese (BMI = 24 ± 3 kg/m2) individuals. Platelet activation status was evaluated by flow cytometry using specific antibodies against the activated platelet membrane glycoprotein IIb/IIIa, p-selectin (CD-62 p), and binding of Annexin-V to platelet anionic phospholipids. Results. Overweight, obese, and morbidly obese females had significantly elevated platelet counts ( P < .0001) compared with normal-weight females. No significant elevation of platelet counts was observed in the male subgroups. A significant age adjusted correlation between BMI and platelet counts ( P < .0001) was found among females. This correlation was attenuated (P = .001) after adjustment for hs-CRP concentrations. The flow cytometry analysis of platelets showed no significant differences in activation marker expression between nonobese and obese individuals. Discussion. Obesity may be associated with elevated platelet counts in females with chronic inflammation. Obesity is not associated with increased platelet activation.

Idiopathic Intracranial Hypertension Is Associated with Lower Body Adiposity

OBJECTIVE To characterize the obesity phenotype(s) in patients with idiopathic intracranial hypertension (IIH). DESIGN Database study. PARTICIPANTS We studied 44 consecutive patients with IIH, in addition to 184 women attending the obesity clinic of the same medical center and 199 obese women participating in the first Israeli national survey on health and nutrition conducted in 1999 and 2000. METHODS Anthropometric parameters were compared with those of 2 control groups of the same age range. MAIN OUTCOME MEASURES Weight, height, and waist and hip circumference were measured. RESULTS Forty subjects, comprising 91.0% of this cohort, were either overweight (body mass index, 25.0-29.9 kg/m(2)) or obese (body mass index > or = 30 kg/m2). Mean waist circumference was 95.3 cm for IIH, 99.8 cm for the national survey, and 114.5 cm for the obesity clinic cohort (P<0.001), whereas hip circumference was 121 cm for IIH, 118.4 cm for the national survey, and 125.8 cm (P = not significant) for the obesity clinic cohorts. Waist-to-hip ratio, a descriptive measure of body fat distribution approximately reflecting upper to lower body fat ratio, was 0.79 in the patients with IIH, 0.84 in the national survey group, and 0.91 in the obesity clinic cohort (P<0.001; all comparisons were adjusted for age and body mass index). CONCLUSIONS In IIH, fat tends to preferentially accumulate in the lower body relative to other obese women of the same range. Whereas most complications of obesity, such as hypertension, diabetes, dyslipidemia, and the metabolic syndrome, are linked to upper body adiposity, IIH may represent a unique condition potentially induced by nonvisceral fat-related mechanisms. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Flow-resistant red blood cell aggregation in morbid obesity

OBJECTIVE: Enhanced red blood cell (RBC) aggregation has an adverse effect on microcirculatory blood flow and tissue oxygenation. It has been previously shown that obesity is associated with increased RBC aggregation. The objectives of the present study were to further characterize obesity-related RBC aggregation and to examine whether the enhanced aggregation is a plasma- or cellular-dependent process.METHODS: Obese (body mass index (BMI)=40±6.3 kg/m2, n=22) and nonobese (BMI=24±3.4 kg/m2, n=18) individuals were evaluated for inflammation markers and aggregation parameters. Aggregation parameters were derived from the distribution of RBC population into aggregate sizes, and from the variation of the distribution as a function of flow-derived shear stress, using a cell flow properties analyzer. To differentiate plasmatic from cellular factors, we determined the aggregation in the presence of autologous plasma or dextran-500kDa and calculated the plasma factor (PF) in the obese group. PF ranges from 0 to 1. When the PF=1, the aggregation is all due to plasmatic factors, when PF=0, the altered aggregation depends entirely on cellular factors, whereas 0<PF<1 reflects the joint contribution of cellular and plasmatic factors.RESULTS: Obese subjects had relatively larger aggregates that were more resistant to dispersion by flow. The calculated PF in the obese group was 0.9, indicating a pronounced contribution of plasma to RBC aggregation in obesity.DISCUSSION: Our results suggest that obese individuals present pathological plasma-dependent RBC aggregation, which is probably triggered by plasma macromolecules associated with the inflammatory response. These findings impact the future attempts to develop strategies aimed at attenuation of the enhanced RBC aggregation in obese individuals.

Attempted Forced Titration of Blood Pressure to <130/85 mm Hg in Type 2 Diabetic Hypertensive Patients in Clinical Practice: The Diastolic Cost

The authors assessed the practicality and results of forced titrating of blood pressure to <130/85 mm Hg based on guidelines of the sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the setting of a clinical practice in 257 diabetic, hypertensive patients. Goal diastolic pressure was achieved in 90% of the patients, but goal systolic pressure was achieved in only 33%. In 57% of the patients, the attained diastolic pressure was ≤70 mm Hg, and in 20% of the cohort diastolic pressure was reduced to <70 mm Hg (mean, 60±1 mm Hg). Patients with final diastolic pressure <70 mm Hg were older, had a higher prevalence of coronary artery disease, and higher initial systolic and pulse pressures compared with patients with final diastolic pressure of 71–85 mm Hg. Thus, attempted lowering of blood pressure to <130/85 mm Hg is associated with excessive lowering of diastolic pressure in a significant number of patients. Whether the benefits of tight systolic control out‐weigh the risks of excessive diastolic reduction requires further prospective assessment.

The appearance of aggregated erythrocytes in the peripheral blood of individuals with insulin resistance

Insulin resistance is associated with low‐grade inflammatory response. The probability that the acute‐phase response is associated with enhanced erythrocyte adhesiveness/aggregation was not explored.

2P-0389 The appearance of aggregated erythrocytes in the peripheral blood of individuals with insulin resistance

BACKGROUND Insulin resistance is associated with low-grade inflammatory response. The probability that the acute-phase response is associated with enhanced erythrocyte adhesiveness/aggregation was not explored. METHODS The degree of erythrocyte adhesiveness/aggregation was evaluated by using a simple slide test. The insulin resistance was evaluated by insulin and glucose concentrations after a night of fasting. The inflammatory response was evaluated by variables of acute-phase response. RESULTS A significant correlation (r = -0.2, p = 0.02) was noted between insulin resistance expressed as the HOMA index and the degree of erythrocyte adhesiveness/aggregation. This was probably due to the concomitant acute-phase response and the presence of increased amounts of inflammation-sensitive proteins that were found to correlate significantly with the degree of erythrocyte adhesiveness/aggregation. In the multiple linear regression analysis, erythrocyte sedimentation rate and fibrinogen concentration but not HOMA index were found to correlate significantly (p < 0.0001 and p = 0.0007 respectively) with the degree of red blood cell adhesiveness/aggregation. CONCLUSIONS Insulin resistance is associated with an enhanced degree of erythrocyte adhesiveness/aggregation and this is related to the presence of enhanced inflammation-sensitive plasma proteins that are part of the acute-phase response. These findings might have hemorheological consequences and might contribute to the pathophysiology of the insulin-resistance syndrome.