Effects of body composition on the procoagulant imbalance in obese patients.

Obesity is associated with increased thrombotic risk and hypercoagulability whose main driver is an excess of coagulation factor VIII relative to protein C. The aims of this study were to evaluate the association between factor VIII, protein C, factor VIII-to-protein C ratio and bioimpedance parameters of body composition in obese patients. We analysed blood from 69 obese patients and 23 non-obese healthy controls. Plasma levels of factor VIII, protein C, and factor VIII-to-protein C ratio were correlated with total fat, visceral fat, and muscle mass. Compared to controls, obese patients had significantly higher factor VIII (110.5% vs 78.05%, p < 0.001), protein C (120.99% versus 110.51%, p = 0.014), and factor VIII-to-protein C ratio (0.93 versus 0.73, p = 0.002). In obese patients, factor VIII correlated with body-mass index, body fat percentage, muscle mass percentage, and fat-to-muscle ratio, whereas protein C had significant relationships with body fat percentage, muscle mass percentage and fat-to-muscle ratio, but not with body-mass index. Factor VIII-to-protein C ratio > 1 was significantly associated with body-mass index (odds ratio 1.08, 95% CI 1.02 to 1.14) and fat-to-muscle ratio (odds ratio 2.47, 95% CI 1.10 to 5.55). Factor VIII-to-protein C ratio strongly correlated with D-dimer levels in the overall population (rho 0.44, p < 0.001) and obese patients (rho 0.41, p < 0.001). In obese patients, bioimpedance measures of body fat and muscle mass percentage were associated with factor VIII and protein C. Factor VIII-to-protein C ratio was strongly associated with fat-to-muscle ratio and only modestly related to BMI.

Non-O blood group and outcomes of in vitro fertilization.

PURPOSE: Retrospective and cross-sectional studies suggested that non-O blood group may be associated with failures of in vitro fertilization (IVF), but data remain controversial. The aim of this observational cohort study was to prospectively evaluate the effect of non-O blood type on clinical outcomes of IVF. METHODS: Women < 40 years who underwent IVF and had ABO blood type recorded as part of the routine workup were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, positive pregnancy test, and clinical pregnancy. RESULTS: A total of 497 women with a mean age of 34.6 (standard deviation 3.2) years were included. The mean number of embryos transferred was 2.3 (standard deviation 0.6). The most common ABO blood types were O (n = 213, 42.9%) and A (n = 203, 40.8%), while 63 (12.7%) and 18 (3.6%) women had the B and AB blood types, respectively. Differences in live birth (21.8 vs. 24.3%, odds ratio [OR] 1.17; 95% confidence intervals [CI], 0.76 to 1.78), positive pregnancy test (37.9 vs. 36.6%, OR 0.96; 95% CI, 0.66 to 1.38), clinical pregnancy (35.1 vs. 33.8%, OR 0.95; 95% CI, 0.66 to 1.39), and spontaneous abortion (12.3 vs. 9.2%, OR 0.72; 95% CI, 0.41 to 1.29) between women with O and non-O blood type were not statistically significant. CONCLUSIONS: In a prospective cohort study, we confirmed the lack of a significant association between non-O blood type and clinical outcomes of IVF. Further studies are needed to clarify whether non-O blood group has any prognostic relevance in women undergoing IVF.

Impaired left ventricular diastolic function and vascular postischemic vasodilation associated with microalbuminuria in IDDM patients.

OBJECTIVE: Microalbuminuria is considered an important predictor of cardiovascular events in diabetic patients. In this study, a possible association of microalbuminuria with significant changes in left ventricular (LV) morphology and function and generalized vascular dysfunction was analyzed in insulin-dependent diabetes mellitus (IDDM) patients without hypertension, coronary artery disease, or autonomic dysfunction. RESEARCH DESIGN AND METHODS: Thirty-four young long-term IDDM patients, 16 with and 18 without microalbuminuria, and 20 control subjects were studied. LV systolic function and wall thickness were evaluated by M-mode echocardiography. LV diastolic function was studied using a combined echo-Doppler and phonocardiographic technique. The hyperemic response to forearm ischemia was measured by strain-gauge plethysmography. All patients underwent 24-h ambulatory blood pressure monitoring. RESULTS: LV mass index and wall thickness:radius ratio were significantly higher in microalbuminuric patients. LV relaxation was significantly impaired in both diabetic groups compared with control subjects; moreover, this impairment was significantly greater in microalbuminuric than in normoalbuminuric patients. In microalbuminuric patients, forearm postischemic vasodilation was also significantly lower and mean awake diastolic blood pressure (dBP) was significantly higher than in the other two groups. CONCLUSIONS: Our data suggest that microalbuminuria is associated with significant changes in LV morphology, a more severe impairment of cardiac diastolic function, altered vascular dilatory capacity, and higher daytime dBP. Therefore, microalbuminuric patients should be considered to have a higher risk of cardiovascular complications and be kept under closer surveillance.

Target organ status and serum lipids in patients with white coat hypertension.

Target organ status and serum lipids were investigated in white coat hypertension in comparison with sustained hypertension and normotension. We selected three groups balanced for sex, age, body mass index, and smoking habit: 50 sustained hypertensives (clinical hypertension and 24-hour ambulatory blood pressure > 135/85 mm Hg, a cutoff limit obtained from a normotensive population), 25 white coat hypertensives (clinical hypertension and 24-hour ambulatory blood pressure < 135/85 mm Hg), and normotensives. Subjects underwent echocardiographic examinations to assess left ventricular mass index, carotid ultrasonography to evaluate intima-media thickness and atherosclerotic plaques, venous occlusion plethysmography to record minimum forearm vascular resistance, and determinations of serum lipid profile and 24-hour urinary albumin excretion. Compared with sustained hypertensives, the white coat hypertensives had significantly lower values of left ventricular mass index (125.9 +/- 20 versus 97.6 +/- 11.5 g/m2, P < .05, intima-media thickness (0.85 +/- 0.18 versus 0.71 +/- 0.15 mm, P < .05), minimum forearm vascular resistance (2.33 +/- 0.11 versus 2.04 +/- 0.08 resistance units, P < .05), urinary albumin excretion values (15.1 +/- 13.8 versus 4.45 +/- 1.48 mg per 24 hours, P < .0001), prevalence of left ventricular hypertrophy (versus 4%, P < .002), intima-media thickening 28% versus 4%, P < .015), and microalbuminuria (22% versus 0%, P < .015). No significant difference, however, was observed between the white coat hypertensives and the normotensives. Serum lipid profile was similar in the white coat hypertensives and in the normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased transforming growth factor-beta production and gene expression by peripheral blood monocytes of hypertensive patients.

Cultured human peripheral blood monocytes are known to secrete and express transforming growth factor-beta (TGF-beta), a multifunctional cytokine that can be involved in myocardial and vascular remodeling. In addition, monocytes/macrophages have been demonstrated to be colocalized with fibrosis of hypertrophied heart and in the vascular wall of hypertensive vessels. In this study, we tested TGF-beta production and mRNA expression in peripheral blood monocytes from hypertensive patients with myocardial hypertrophy and increased carotid myointimal thickness with respect to healthy normotensive control subjects. We found an increased TGF-beta activity in the conditioned medium of monocytes from hypertensive patients compared with control subjects as evaluated by inhibition of [3H]thymidine incorporation by mink lung epithelial cells (-83% and -18% in hypertensive and normotensive subjects; P<.001). Western blot analysis confirmed a significant difference in the amount of TGF-beta protein secreted in the conditioned medium of hypertensive patients compared with that of normotensive subjects. Finally, we also observed a 4.2- and 5.5-fold increase in the amount of TGF-beta1 and TGF-beta2 transcripts, respectively. Our results indicate an upregulation of the TGF-beta system in the peripheral blood monocytes of hypertensive patients with cardiovascular structural changes, suggesting a possible role of TGF-beta monocyte production in hypertensive disease.

Vascular changes in hypertensive patients with different left ventricular geometry.

OBJECTIVE: To evaluate vascular structural changes in hypertensive patients with different patterns of left ventricular geometry. DESIGN AND METHODS: From 250 untreated hypertensive patients who underwent ambulatory blood pressure monitoring and echocardiographic study, we selected four groups matched for sex, age, body mass index, smoking habits and serum lipid values: 25 hypertensive subjects with normal left ventricular geometry, 16 with concentric left ventricular remodeling, 26 with concentric left ventricular hypertrophy and 18 with eccentric non-dilated left ventricular hypertrophy. These patients underwent carotid ultrasonography to evaluate the intimal-medial thickness and lumen diameter, and venous occlusion plethysmography to record minimum forearm vascular resistance (an index of arteriolar structural changes). RESULTS: The intimal-medial thickness and minimum forearm vascular resistance were significantly higher (both P<0.05) in hypertensive subjects with concentric left ventricular remodeling (0.95 mm, 2.68 RU) and concentric left ventricular hypertrophy (0.96 mm, 2.71 RU) than in those with eccentric non-dilated left ventricular hypertrophy (0.81 mm, 2.36 RU) and normal left ventricular geometry (0.71 mm, 2.15 RU). There was no difference between hypertensive patients with concentric left ventricular remodeling and concentric left ventricular hypertrophy. The intimal-medial thickness and minimum forearm vascular resistance tended to be higher in hypertensive subjects with eccentric non-dilated left ventricular hypertrophy than in those with normal left ventricular geometry, but this difference did not attain statistical significance. CONCLUSIONS: This study shows that the spectrum of cardiac adaptation to hypertension is associated with a spectrum of vascular adaptation which might be related both to hemodynamic stimuli and differences in the expression or activity of vascular growth factors.

Haemostatic abnormalities, cardiac involvement and serum tumor necrosis factor levels in X-linked dystrophic patients.

Left ventricular thrombosis and systemic emboli have been demonstrated to complicate cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD). We investigated plasma levels of prothrombin fragment 1+2 (F1+2). thrombin-antithrombin III complex (TAT) and circulating levels of tumor necrosis factor-alpha (TNF-alpha), a procoagulant cytokine that has been shown to be elevated in patients with depressed cardiac function, in 20 patients with DMD and 12 patients with BMD as compared with 30 age-matched control subjects. Significantly elevated levels of F1+2 (DMD: 1.4+/-0.8 nmol/l; BMD: 1.8+/-0.8 nmol/l vs. controls: 0.7+/-0.2 nmol/l, p <0.01 and p <0.001, respectively), TAT complexes (DMD: 4.7+/-2.7 microg/l, BMD: 5+/-2.3 microg/l vs. controls: 1.6+/-0.5 microg/l, p <0.001) and TNF-alpha (54+/-9 vs. 25+/-7 pg/ml, p <0.001) were observed in patients with the dystrophic disease compared to control subjects. A significantly negative correlation was also found between F1+2 and TAT complexes and left ventricular ejection fraction (r = -0.65, p <0.0001; r = -0.80, p < 0.0001, respectively) and a positive correlation between F1+2 and TAT complexes and serum TNF-alpha levels (r = 0.67, p <0.0001; r = 0.70, p <0.0001, respectively). Our results indicate a hypercoagulable state in X-linked dystrophic patients. A possible relationship between haemostatic activation, left ventricular dysfunction and TNF-alpha system upregulation may be suggested.

Mechanism of isoproterenol-induced angina pectoris in patients with obstructive hypertrophic cardiomyopathy and normal coronary arteries.

In 14 patients with obstructive hypertrophic cardiomyopathy and angiographically normal coronary arteries, 8 with angina (group B) and 6 without (group A), the effects of intravenous isoproterenol, 2 to 4 micrograms/min, followed by intravenous propranolol, 0.2 mg/kg, were studied. An intraventricular systolic gradient less than 50 mm Hg, high-quality echocardiograms and cineangiograms and high-fidelity pressure tracings were selection criteria. Hemodynamic and metabolic variables were assessed during basal conditions, after 5 minutes of isoproterenol infusion or at angina and ST-segment depression, and 5 and 10 minutes after intravenous propranolol infusion. Isoproterenol increased the intraventricular systolic gradient more significantly in group B than in group A (102.4 +/- 8.3 vs 52.2 +/- 8.2, p less than 0.0001). Group B also had higher left ventricular end-diastolic pressure (32.5 +/- 3.9 vs 20.2 +/- 5.7), lower mean arterial pressure (69.7 +/- 3.5 vs 84.7 +/- 4.8) and a smaller increase in coronary sinus flow (176.1 +/- 9.2 vs 261.5 +/- 33.9, all p less than 0.0001), concomitant with lactate release and ST-segment depression. Propranolol promptly reversed hemodynamic and metabolic changes caused by isoproterenol, except for a further coronary sinus flow increase (from 176.1 +/- 9.2 to 219 +/- 14.2 ml/min, p less than 0.001), and heart rate decrease below basal values (57.8 +/- 7.5 vs 79.9 +/- 9.8 beats/min, p less than 0.001) in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial disease in dipper and nondipper hypertensive patients.

Carotid artery and small vessel structural changes were evaluated in 45 dipper and 45 nondipper hypertensive subjects matched for sex, age, body mass index, smoking habit, and serum lipids. Patients underwent carotid ultrasonography to evaluate lumen diameter, intima-media thickness, cross-sectional area, and atherosclerotic plaques, and plethysmographic examination to record minimum forearm vascular resistance. In the whole study population, carotid cross-sectional area and prevalence of atherosclerotic plaques tended to be higher in nondippers than in dippers (19.9 +/- 6.0 v 17.5 +/- 6.1 mm2, P = .07, and 40% v 26%, P = .18), whereas intima-media thickness and minimum forearm vascular resistance were significantly higher in nondippers than in dippers (0.89 +/- 0.12 v 0.8 +/- 0.15 mm, P < .02, and 2.53 +/- 0.3 v 2.34 +/- 0.3 arbitrary resistance units (RU), P < .02). When gender was taken into account, different results were obtained in men and women. In men, vascular characteristics were not significantly different between dippers and nondippers. In women, carotid cross-sectional area and prevalence of atherosclerotic plaques tended to be higher in nondippers than in dippers (18.3 +/- 4.9 v 15.5 +/- 4.5 mm2, P = .06, and 40% v 15%, P = .15), and intima-media thickness and minimum forearm vascular resistance were significantly higher in nondippers than in dippers both before (0.84 +/- 0.1 v 0.73 +/- 0.1 mm, P < .01, and 2.38 +/- 0.3 v 2.16 +/- 0.2 RU, P < .01) and after adjustment for 24-h blood pressure. In conclusion, our data suggest that the progression of vascular disease may be differently affected in the two sexes by a different circadian blood pressure profile.

Captopril therapy in severe hypertension: effects of intravenous administration.

In 10 severe hypertensives the effects of intravenous administration of scalar doses of captopril were evaluated. The behaviour of blood pressure, heart rate, electrocardiographic pattern and left ventricular (LV) diastolic function, in basal condition (T0) and after 60 min of captopril infusion (T60), were analysed. Diastolic performance was assessed by pulsed wave Doppler echocardiography, evaluating transmitral peak flow velocities in early diastole (PEDV), late diastole (PLDV) and the PEDV/PLDV ratio. All patients showed an increase in LV mass (assessed by M-mode echocardiography) and altered diastolic performance, documented by high PLDV and low PLDV/PEDV ratio values. Clinical, haematological, urinary and biochemical data were also assessed for possible side effects. Captopril significantly reduced BP in 7 out of the 10 patients. Supine BP decreased from 212 +/- 15.3/126 +/- 5.6 to 171 +/- 17.7/98 +/- 11.8 mmHg (T0 vs. T60 P less than 0.0001). No electrocardiographic abnormality was observed during the study. The goal of antihypertensive effect was reached at 40-50 min after the onset of captopril therapy. Heart rate showed a small but constant decrease (from 76 +/- 7.7 to 72.8 +/- 5.7 beats/min, T0 vs. T60, P less than 0.05). Side effects of intravenous captopril were always mild and transient; no severe hypotension as 'first dose effect' was observed in our study. The echocardiographic data showed a significant decrease in LV end-systolic dimension after captopril infusion, while left atrial, LV diastolic dimension and fractional shortening remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of the cardiovascular effects of clenbuterol in exercise-induced asthma.

The protective effect of clenbuterol on exercise-induced asthma was studied in 14 patients with aspecific bronchial hyperreactivity. The selectivity of clenbuterol for beta 2-receptors was also studied. Patients were selected according to spirometric criteria: reduced dynamic indexes of respiratory function after exercise and, particularly, forced expiratory volume at 1 s (FEV1) decreased by at least 20% compared with initial values. A polycardiographic study was simultaneously carried out for the evaluation of systolic time intervals and polycardiographic indexes (Weissler index, Blumberger index and QT/QS2 index). After the preliminary measurements (C1), oral clenbuterol was started (0.02 mg X 2/day) and measurements were repeated after 30 (CII) and 60 days (CIII) of therapy. During treatment, physical exercise did not significantly influence the indexes of respiratory function (FEV1 decreased by 4.7 +/- 5.8 and 9.8 +/- 10.5% in CII and CIII with respect to initial values). Similarly systolic time intervals and polycardiographic indexes did not change significantly with respect to the initial values. A small increase in heart rate at rest was observed in CII (+ 7%, p less than 0.05): however, no significant changes were recorded in CIII compared with the initial values. Clenbuterol thus seems to offer an effective protection against exercise-induced asthma without the negative effects on the cardiovascular system which may arise from activation of beta 1-adrenergic receptors.

Lactate release during the recovery period of pacing-induced angina in assessment of myocardial ischaemia.

Myocardial lactate (L) metabolism was tested in 27 stable angina patients during atrial pacing (AP) and in the recovery period (R) from AP-induced angina pectoris. The recovery period was assessed in order to evaluate the changes in the rate of L release and detect possible relationships with the severity of ischaemic damage. The following variables were assessed: coronary sinus blood flow (CSBF), left ventricular end-diastolic pressure (LVEDP), lactate extraction ratio (L%), lactate extraction or release rate (LR) and myocardial oxygen consumption (MVO2) at the onset of AP (AP1), during angina (AP2), and 30 s, 2 and 4 min (R1, R2 and R3) after AP ceased. At Ap2, negative L% and LR values (-39.37 +/- 43.3, -3.2 +/- 2.9) were found, in spite of a rise in CSBF (+86%, P less than 0.001). Furthermore, LVEDP showed its maximal increase in AP2 (+27%, P less than 0.001). Compared to AP2, L% resulted unchanged in R1, while LR showed a mild decrease (from -3.2 +/- 2.9 to +2.06 +/- 2.93). Lactate production was converted to extraction in R3 only. Since lactate production and release are progressively reduced with increasing severity of ischaemic damage, AP2 coronary sinus lactate release should largely arise from the less damaged areas (i.e. the outer myocardial layers) and the contribution of the more damaged areas (i.e. the inner myocardial layers) should be more limited. After AP ceases, the mild ischaemic areas should recover more rapidly than the severely ischaemic areas, where the damage only declines, leading to a temporary increase in lactate production and release.(ABSTRACT TRUNCATED AT 250 WORDS)

'White-coat' hypertension in patients with newly diagnosed hypertension: evaluation of prevalence by ambulatory monitoring and impact on cost of health care.

To evaluate the prevalence of 'white-coat' hypertension in patients with newly diagnosed hypertension, 255 subjects (131 males and 124 females) underwent 24-h ambulatory blood pressure monitoring. Patients with 24-h systolic and diastolic blood pressure < 135/85 mmHg were classified as white-coat hypertensives and the remaining as sustained hypertensives. On the assumption that white-coat hypertensives may not need to take antihypertensive medication, we evaluated the impact on cost of health care of two strategies based essentially on treating all patients according to casual blood pressure, or ambulatory blood pressure monitoring, followed by drug treatment in sustained hypertensives only. Of the 255 hypertensives studied, 54 (21%), confidence interval 16%, 26%, were classified as white-coat hypertensives. The age, sex-ratio and body mass index did not differ between the white-coat and the sustained hypertensive subjects. The strategy of monitoring all patients and of treating only the sustained hypertensives resulted in a substantial coat saving, which was calculated to be about 110,000 U.S.A. dollars over a period of 6 years. In conclusion, white-coat hypertensives are frequent among patients with newly diagnosed hypertension, and they do not differ from sustained hypertensives as regards demographic data. Ambulatory blood pressure monitoring, when used to decide whether or not to treat pharmacologically, increases the cost-effectiveness of treatment for hypertension and reduces the cost of health care.

Increased systemic oxidative stress after elective endarterectomy: relation to vascular healing and remodeling.

It has been reported that systemic and local redox state may have an important role in the functional and organic changes characterizing the process of vascular response to injury. Carotid endarterectomy to remove atherosclerotic plaque is followed by a long lasting healing and remodeling process that can be carefully followed over time with noninvasive ultrasonography. Plasma vitamin C concentration and native LDL (n-LDL) content in lipid peroxides, vitamin E, beta-carotene, and lycopene as well as LDL susceptibility to peroxidation were assessed in 45 patients undergoing elective endarterectomy for internal carotid stenosis, at baseline, 24 hours, 3 and 15 days, and 1 month after surgery. Serial duplex scans were performed in all patients postoperatively and 3, 6, and 12 months. The changes in far wall thickness (FW) and % renarrowing from postoperatively to 12 months were used as remodeling indices. Plasma antioxidant vitamins and lag-phase showed a sharp and significant decrease during the first 24-hours after surgery remaining unchanged until the third day, whereas, an opposite trend was evidenced for n-LDL content in lipid peroxides and serum ceruloplasmin. After the third day all the parameters returned progressively to baseline within one month from endarterectomy. Interestingly, the n-LDL lipid peroxide content, the serum ceruloplasmin and the plasma vitamin C concentration, measured at 24 and 3 days from surgery, were significantly associated to the change in % renarrowing from postoperatively to 12 months. The higher the LDL content in lipid peroxides, the higher the serum level of ceruloplasmin, the lower the plasma content in vitamin C and the higher the % of vessel renarrowing. In conclusion, carotid endarterectomy with atherosclerotic plaque removal is associated with an acute and prolonged increase in systemic oxidative stress that influences vascular healing and late luminal loss.