Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients

Aim

Advanced research has radically changed both diagnosis and treatment of diabetes during last three decades; a number of classes of oral antidiabetic agents are currently available for better glycemic control. Present study aims to evaluate the effect of metformin on different stress and inflammatory parameters in diabetic subjects.

Methods

208 type 2 diabetes patients were randomly assigned for metformin and placebo.

Results

Reactive oxygen species generation, advanced oxidation protein products (179.65 ± 13.6, 120.65 ± 10.5 μmol/l) and pentosidine (107 ± 10.4, 78 ± 7.6 pmol/ml) were found to be reduced by metformin treatment compared to placebo. On the other hand metformin administration enhanced total thiol and nitric oxide level (p < 0.05). But nutrient level (Mg⁺², Ca⁺²) in plasma was not altered by the treatment. Significant restoration of C reactive protein (p < 0.05) was noticed after metformin therapy. Metformin administration also improved Na⁺K⁺ATPase activity (0.28 ± 0.08, 0.41 ± 0.07 μmol Pi/mg/h) in erythrocyte membrane.

Conclusions

This study explores that metformin treatment restores the antioxidant status, enzymatic activity and inflammatory parameters in type 2 diabetic patients. Metformin therapy improves the status of oxidative and nitrosative stress altered in type 2 diabetes. This study unfolds the cardio protective role of metformin as an oral hypoglycemic agent.     

Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome

Objective

Metabolic syndrome (MetS) is associated with cardiovascular disease (CVD). Insulin resistance has been hypothesized as the underlying feature of MetS. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely used antihypertensives that may improve insulin sensitivity. The aim of the study is to evaluate the effect of ACEI/ARB on incident CVD events in older hypertensive patients with MetS.

Materials/Methods

We used the Cardiovascular Health Study, a prospective cohort study of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.

Results

ACEI/ARB use was associated with a decreased risk of CVD events (adjusted HR = 0.658, 95 % C.I. [0.436–0.993]) compared to other antihypertensives. When CVD endpoints were evaluated separately, use of ACEI/ARB was associated with lower rates of angioplasty and coronary events (HR of 0.129 and 0.530 respectively, with 95 % CI [0.017–0.952] and [0.321–0.875]).

Conclusions

ACEI/ARB use was associated with a lower risk of CVD events in older hypertensive patients with MetS, primarily due to a reduction in coronary events. The potential protective effect of ACEI/ARB on CVD events in older individuals with MetS will need further confirmation from prospective studies.     

Melatonin reduces night blood pressure in patients with nocturnal hypertension

Purpose

Nocturnal hypertension is associated with a high risk of morbidity and mortality. A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients. We therefore studied the potency of melatonin to reduce nighttime blood pressure (BP) in treated hypertensive patients with nocturnal hypertension.

Patients and Methods

Thirty-eight treated hypertensive patients (22 males, mean age 64 ± 11 years) with confirmed nocturnal hypertension (mean nighttime systolic BP >125 mm Hg), according to repeated 24-hour ambulatory blood pressure monitoring (ABPM), were randomized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks. A 24-hour ABPM was then performed.

Results

Melatonin treatment reduced nocturnal systolic BP significantly from 136 ± 9 to 130 ± 10 mm Hg (P = .011), and diastolic BP from 72 ± 11 to 69 ± 9 mm Hg (P = .002), whereas placebo had no effect on nocturnal BP. The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo (P = .01), and was most prominent between 2:00 am and 5:00 am (P = .002).

Conclusions

Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension. Thus, an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension.     

Echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction: role of mitral regurgitation

Introduction and objectives

Patients with heart failure and similar left ventricular systolic dysfunction have differing exercise capacity. The aim of this study was to identify echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction.

Methods

We included 150 patients with class II (70%) or III (30%) heart failure with left ventricular ejection fraction below 40%. Six-minute walking test and cardiac color Doppler-echo, including tissue Doppler of mitral and tricuspid rings, were performed. Moderate and severe mitral regurgitation were considered as significant. Two groups were divided according to the median walking distance (290 m): Group 1, <290 m and Group 2, ≥290 m.

Results

Mitral regurgitation was detected in 112 patients (75%), which was significant in 40 (27%). Group 1 showed more significant mitral regurgitation (35 vs 18%), increased left atrium area (27±1 vs 24±1 cm²), mitral E amplitude (88±5 vs 72±3 cm/s) and systolic pulmonary pressure (37±1 vs 32±1 mmHg, all P<.05). By logistic regression analysis, only the presence of significant mitral regurgitation was independently associated with less walked distance (odds ratio: 3.44 95% confidence interval 1.02-11.66, P<.05). By multiple linear regression, the only independent predictor of walked distance was left atrium area (r=0.25, beta coefficient: −6.52 ± 2, P<.01).

Conclusions

In patients with class II-III heart failure and left ventricular systolic dysfunction, the main echocardiographic predictors of exercise capacity are related to the presence of significant mitral regurgitation.Full English text available from:www.revespcardiol.org     

Effects of low doses of casein hydrolysate on post-challenge glucose and insulin levels

Background

Ingestion of high doses of casein hydrolysate stimulates insulin secretion in healthy subjects and patients with type 2 diabetes. The effects of low doses have not been studied. The aim of this study was to assess the effect of lower doses of a casein hydrolysate on the glucose and insulin responses to an oral glucose tolerance test in patients with type 2 diabetes.

Methods

In this randomized, placebo-controlled, double-blind study, thirteen patients with type 2 diabetes (age: 58 ± 1 years) were studied.Glucose, insulin and C-peptide responses were determined after the oral administration of 0 (control), 6 or 12 g protein hydrolysate in combination with 50 g carbohydrate.

Results

Twelve grams of casein hydrolysate, but not 6 g, elevated insulin levels and decreased glucose levels post-challenge. These changes over time were not large enough to also affect the total area under the curve of glucose and insulin. C-peptide levels did not change after both treatments.

Conclusion

Ingestion of six grams of casein hydrolysate did not affect glucose or insulin responses. Intake of 12 g of casein hydrolysate has a small positive effect on post-challenge insulin and glucose levels in patients with type 2 diabetes.     

Exercise blood pressure response, albuminuria, and arterial stiffness in hypertension

Background

A hypertensive response to exercise is associated with high cardiovascular risk, whereas the data about its relation to surrogates of subclinical atherosclerosis are scarce. We investigated the relationships of a hypertensive response to exercise with urinary albumin excretion and arterial stiffness in hypertensives.

Methods

There were 171 untreated males (mean age 52 years, all Caucasian) with stage I-II essential hypertension and a negative treadmill exercise test divided into those with a hypertensive response to exercise (n = 48) (peak exercise systolic blood pressure ≥210 mm Hg) and to those with normal blood pressure response (n = 123). Albumin-to-creatinine ratio values were determined as the mean of 3 nonconsecutive morning spot urine samples, and arterial stiffness was evaluated on the basis of carotid-to-femoral pulse wave velocity.

Results

Patients with a hypertensive response to exercise compared with those with normal blood pressure response exhibited greater log albumin-to-creatinine ratio (1.52 ± 0.59 vs 0.97 ± 0.33 mg/g) and higher pulse wave velocity (8.7 ± 1.6 vs 7.7 ± 1.2 m/s), independent of potentially confounding demographic and clinical factors. Resting systolic blood pressure (odds ratio [OR] 1.11, 95% confidence interval [CI], 1.06-1.16), body mass index (OR 1.12, 95% CI, 1.02-1.23), resting heart rate (OR 0.96, 95% CI, 0.93-0.99), and albumin-to-creatinine ratio (OR 7.45, 95% CI, 2.54-21.83) were independently associated with a hypertensive response to exercise.

Conclusion

A hypertensive response to exercise is related to augmented albumin-to-creatinine ratio and arterial stiffness, reflecting accelerated subclinical atherosclerosis. The association of albumin excretion with exercise blood pressure response suggests that albuminuria constitutes an important factor in the interpretation of the hypertensive response to exercise-associated risk.     

Impairment of insulin action in non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients

Aims

To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

Methods

12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI < 25 kg/m²). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively.

Results

The first-phase insulin release did not differ between the ERDM and control subjects (p = 0.532), while the acute insulin response was absent in the DM-2 patients (p = 0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1 mg/kg·min, p = 0.000) and DM-2 (9.6 ± 1.1 mg/kg·min, p = 0.000) groups than that in the control group (13.2 ± 1.2 mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p = 0.110). Fasting FFA levels of the ERDM (p = 0.007) and DM-2 (p = 0.000) subjects were significantly higher than those of the controls.

Conclusions

Non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.     

Erythrocyte Na+-Li+ counter-transport activity and digoxin-like substances in insulin dependent diabetic women with preexisting preeclampsia

Aim of the study

To determine whether there is pathogenetic link between red cells sodium-lithium counter-transport activity and digoxin-like immunoreactive substances (DLIS) in plasma of insulin-dependent diabetic (IDDM) and non-diabetic women with preexisting preeclampsia (PE).

Subjects and methods

We studied Na⁺/Li⁺ CT activity in red cells and plasma levels of DLIS in 11 IDDM women with preexisting PE (Group 1), 13 IDDM without preexisting PE (Group 2) 23 non-diabetic women with preexisting PE (Group 3) and 12 non-diabetic women with normal pregnancy (Group 4) at least 4 months after delivery.

Results

Na⁺/Li⁺ CT activity was higher in Group 1 compared to Group 2 (mean ± SEM 0.316 ± 0.05 vs 0.190 ± 0.02 mmol/LRBC/hr p < 0.05) and in Group 3 compared to Group 4 (0.365 ± 0.004 vs 0.168 ± 0.01 mmol/LRBC/hr, p < 0.01). Plasma levels of DLIS were higher in Group 3 compared to Group 4 (0.727 ± 0.189 vs 0.295 ± 0.066 ng/ml; p < 0.05); there was no statistically significant difference between the two diabetic groups. In Groups 1 and 3, Na⁺/Li⁺ CT activity was correlated to the plasma levels of DLIS (r = 0.927; p < 0.001 and r = 0.485; p < 0.05 respectively).

Conclusion

Increased Na⁺/Li⁺ CT activity and increased plasma levels of DLIS may contribute to PE in IDDM and non-diabetic women.     

Comparison between arterial and capillary blood glucose monitoring in patients with shock

Background

The accuracy of bedside glucometry using capillary blood is contentious in patients admitted to intensive care units. We aimed to compare the accuracy of capillary bedside glucometry with arterial samples in critically ill patients with shock through a prospective case-control study.

Methods

Study group consisted of 100 patients with shock on vasopressor support and control group had 100 normotensive patients. Arterial and capillary samples were taken simultaneously and were tested immediately at the bedside. Results of the paired measurements were analyzed as a scatter plot by Bland and Altman method and were expressed as a correlation coefficient. Values were considered to disagree significantly when the difference exceeded 20%.

Results

Mean arterial and capillary sugars (mg/dl) in study and control groups were 164.7 ± 70 and 157.4 ± 68.9, and 167.1 ± 62.2 and 167.5 ± 61, respectively. On Bland-Altman analysis, 6% in study group and 5% in control group were out of range (acceptable limit < 5%). Correlation between capillary and arterial values was less in the study group (r = 0.917, p < 0.001 vs r = 0.979, p < 0.001). In addition, the disagreement between capillary and arterial values was more than 20% in 18% of the patients in the study group vs 3% in control group (p = 0.015) (ISO standard < 5%).

Conclusions

Capillary blood glucose monitoring is reliable only in a selected group of ICU patients. Hence, caution must be exercised especially in patients with shock in whom arterial blood may be preferred.     

Minimum salvaged myocardium after rescue percutaneous coronary intervention: quantification by cardiac magnetic resonance

Introduction and objectives

When fibrinolysis fails in patients with ST elevation myocardial infarction, they are referred for a rescue percutaneous coronary intervention (PCI). However, there is still no evidence of how much myocardium potentially at risk we can actually salvage after rescue PCI.

Methods

Fifty consecutive patients. Cardiac magnetic resonance was performed within 6 days. Myocardial necrosis was defined by the extent of abnormal late enhancement, myocardium at risk by extent of edema, and the amount of salvaged myocardium by the difference between myocardium at risk and myocardial necrosis. Finally, myocardial salvage index (MSI) resulted from the fraction (area-at-risk minus infarct-size)/area-at-risk.

Results

The mean time elapsed between pain onset and fibrinolitic agent administration was 176 ± 113 min; time lysis-rescue = PCI 209 ± 122 min; time pain onset-PCI = 390 ± 152 min. The area at risk was 37% ± 13% and infarct size 34.5% ± 13%. Salvaged myocardium was 3% ± 4% and MSI 9 ± 8. Salvaged myocardium and MSI were similar between patients with the artery open on arrival at the catheterization lab (Thrombolysis in Myocardial Infarction [TIMI] 3) and those with TIMI flow ≤2 (3.3% ± 3.6% and 8.2 ± 6.9 in TIMI 0-2 vs 3.0% ± 3.7% and 10.8 ± 10.9 in TIMI 3; P = .80 and 0.31, respectively). No significant difference was observed between patients who went through rescue PCI within a shorter time and those with longer delay times.

Conclusions

The myocardial salvage after rescue PCI quantified by cardiac magnetic resonance is very small. The long delay times between pain onset and the opening of the infarct-related artery with PCI are most probably the reason for such a minimal effect of rescue PCI.Full English text available from: www.revespcardiol.org     

N-acetylcysteine attenuates leukocytic inflammation and microvascular perfusion failure in critically ischemic random pattern flaps

Introduction

Microcirculatory dysfunction causes ischemia resulting in tissue necrosis. N-acetylcysteine (NAC) has been shown capable of protecting tissue from ischemic necrosis. However, the mechanism of action of NAC is yet not fully understood.

Objective

Herein, we studied whether NAC is capable of attenuating microvascular perfusion failure in critically ischemic musculo-cutaneous tissue.

Material and methods

A laterally based skin flap was elevated in the dorsum of C57BL/6 mice and fixed into a dorsal skinfold chamber. Arteriolar perfusion, functional capillary density, leukocytic inflammation, apoptotic cell death, and non-perfused tissue area were repetitively analyzed over 10 days by intravital fluorescence microscopy. Treatment with either 100 mg/kg NAC or saline (control) was started 30 min before surgery and was continued until day 10 after flap elevation.

Results

Surgery induced leukocytic inflammation, microvascular perfusion failure, apoptosis, and tissue perfusion failure. NAC was capable of significantly attenuating the area of non-perfused tissue. This was associated by a marked arteriolar dilation and an increased capillary perfusion. NAC further reduced the ischemia-associated leukocytic response and significantly attenuated apoptotic cell death in all areas of the flap.

Conclusion

NAC is effective to attenuate leukocytic inflammation and microvascular perfusion failure in critically ischemic tissue. Thus, NAC treatment may represent a promising approach to improve the outcome of ischemically endangered flap tissue.     

Sub-clinical organ damage in hypertension and obesity

Background

The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients.

Aim and methods

We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients.

Results

There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs7%, χ² 5.8, P = 0.0157) and carotid abnormalities (53 vs 10%, χ² 69.5, P < 0.0001) as well as higher urinary albumin excretion rate (−0.05 ± 0.52 vs −0.28 ± 0.43log ACR, P < 0.0001) and carotid intima-media thickness (0.955 ± 0.224 vs 0.681 ± 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively.

Conclusions

Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.     

Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats

Background

Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats.

Methods

Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17β-oestradiol (E2) supplements (10 μg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement).

Results

In oophorectomised rats plasma levels of E2 declined from 1301 ± 80 to 196 ± 48 pmol/L (p < 0.01) and cardiac expression of oestrogen receptors (ER) decreased by ∼ 60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 ± 2.0 to 6.0 ± 0.3 ng/mL, p < 0.01), minimised infarction (from 37.0 ± 1.2% to 18.1 ± 2.3%, p < 0.05), increased SBP (from 82 ± 4.2 to 97 ± 4.4 mm Hg, p < 0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion.

Conclusion

Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90⁺ stem cells may be involved.     

One-week and 6-month cardiovascular magnetic resonance outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusion of ST-segment elevation myocardial infarction

Introduction and objectives

Pharmacoinvasive strategy represents an attractive alternative to primary angioplasty. Using cardiovascular magnetic resonance imaging we compared the left ventricular outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusion of ST-segment elevation myocardial infarction.

Methods

Cardiovascular magnetic resonance was performed 1 week and 6 months after infarction in two consecutive cohorts of patients included in a prospective university hospital ST-segment elevation myocardial infarction registry. During the period 2004-2006, 151 patients were treated with pharmacoinvasive strategy (thrombolysis followed by routine non-immediate angioplasty). During the period 2007-2008, 93 patients were treated with primary angioplasty. A propensity score matched population was also evaluated.

Results

At 1-week cardiovascular magnetic resonance, pharmacoinvasive strategy and primary angioplasty patients showed a similar extent of area at risk (29 ± 15 vs. 29 ± 17%, P = .9). Non-significant differences were detected by cardiovascular magnetic resonance at 1 week and at 6 months in infarct size, salvaged myocardium, microvascular obstruction, ejection fraction, end-diastolic volume index and end-systolic volume index (P > .2 in all cases). The same trend was observed in 1-to-1 propensity score matched patients. The rate of major adverse cardiac events (death and/or re-infarction) at 1 year was 6% in pharmacoinvasive strategy and 7% in primary angioplasty patients (P = .7).

Conclusions

A pharmacoinvasive strategy including thrombolysis and routine non-immediate angioplasty represents a widely available and logistically attractive approach that yields identical short-term and long-term cardiovascular magnetic resonance-derived left ventricular outcome compared to primary angioplasty.Full English text available from:www.revespcardiol.org     

Les réponses sympathiques dans l’hypertension artérielle essentielle

High blood pressure (BP) is a major cause of cardiovascular disease and primary hypertension is a frequent pathological condition. Sympathetic hyperactivity may be involved in primary hypertension. The purpose of this study was mainly to evaluate sympathetic activity when performing cardiovascular autonomic profile examination in patients with primary hypertension in comparison with normotensive subjects.

Patients and methods

This prospective study included one group of hypertensive patients (n = 120, mean age 54 years) compared with a control group (n = 120, mean age 52 years) of normotensive subjects. Autonomic tests included deep-breathing (DB), hand-grip (HG) and echostress test (ES). Comparison tests between the two groups, similar in age, were expressed as mean ± SE and made using the t Student test, p < 0.05 was considered significant.

Results

Alpha-adrenergic sympathetic response using ES method produced a BP response of 20,0% ± 9,8 in hypertensive patients group and 15,2% ± 8,6 in the control group (p < 0.001). Alpha-adrenergic sympathetic response using three minutes HG test was of 16,7% ± 7,5 in hypertensive patients group and 13,3% ± 6,5 in the control group (p < 0.001). Vagal stimulation in hypertensive group after DB showed that electrocardiographic: ECG (EKG) waves R (RR) interval variation was of 30,2% ± 8,1 meanwhile in the control group this RR variation was of 46,1% ± 21,1 p < 0.001, and the one of HG of 15 seconds was 17,6% ± 10,2 versus 32,5% ± 12,7 p < 0.001.

Conclusion

Hypertensive patients had a significantly higher sympathetic response to central and peripheral stimulations and a significantly lower parasympathetic response when compared to normotensive controls.     

Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease

Background

Sudden cardiovascular death is increased in chronic kidney disease (CKD). Experimental CKD models suggest that angiogenesis and nitric oxide (NO) inhibitors induce myocardial fibrosis and microvascular dropout thereby facilitating arrhythmogenesis. We undertook this study to characterize associations of CKD with human myocardial pathology, NO-related circulating angiogenesis inhibitors, and endothelial cell behavior.

Methods

We compared heart (n = 54) and serum (n = 162) samples from individuals with and without CKD, and assessed effects of serum on human coronary artery endothelial cells (HCAECs) in vitro. Left ventricular fibrosis and capillary density were quantified in post-mortem samples. Endothelial to mesenchymal transition (EndMT) was assessed by immunostaining of post-mortem samples and RNA expression in heart tissue obtained during cardiac surgery. Circulating asymmetric dimethylarginine (ADMA), endostatin (END), angiopoietin-2 (ANG), and thrombospondin-2 (TSP) were measured, and the effect of these factors and of subject serum on proliferation, apoptosis, and EndMT of HCAEC was analyzed.

Results

Cardiac fibrosis increased 12% and 77% in stage 3–4 CKD and ESRD and microvascular density decreased 12% and 16% vs. preserved renal function. EndMT-derived fibroblast proportion was 17% higher in stage 3–4 CKD and ESRD (P_trend = 0.02). ADMA, ANG, TSP, and END concentrations increased in CKD. Both individual factors and CKD serum increased HCAEC apoptosis (P = 0.02), decreased proliferation (P = 0.03), and induced EndMT.

Conclusions

CKD is associated with an increase in circulating angiogenesis and NO inhibitors, which impact proliferation and apoptosis of cardiac endothelial cells and promote EndMT, leading to cardiac fibrosis and capillary rarefaction. These processes may play key roles in CKD-associated CV disease.     

Indexes of β-cell function from the oral glucose tolerance test can modestly predict pancreatic β-cell area in Korean

Aims

Pancreatic β-cell function indexes have been suggested using the oral glucose tolerance test (OGTT). Here, we investigated whether β-cell function index from the OGTT reflects pancreatic β-cell area in Korean patients.

Methods

The study consisted of 45 patients who underwent pancreatectomies. Before operation, a 75-g OGTT was performed. Immunohistochemical staining was performed, and indexes of β-cell function from the OGTT data were compared with the pancreatic β-cell area.

Results

The β-cell area of the pancreas was 1.07 ± 0.33% in the normal glucose tolerance group, 1.71 ± 0.85% in the pre-diabetes group (impaired glucose tolerance and impaired fasting glucose), and 1.08 ± 0.57% in the diabetes group. The β-cell area of the pre-diabetes group was significantly higher than that of the diabetes group. Pancreatic β-cell area showed a significant correlation with a homeostasis model assessment of β-cell function (r = 0.358, P = 0.016), disposition index (r = 0.336, P = 0.024), fasting glucose (r = −0.359, P = 0.015), and the C-peptide/glucose 30 min ratio (r = 0.319, P = 0.035).

Conclusions

Some parameters of β-cell function from the OGTT showed a significant relationship with the β-cell area of pancreas.     

Optimising management of hypertension in primary care: the Valsartan Intensified Primary Care Reduction of Blood Pressure (Viper-Bp) study

Background

The Valstartan Intensified Primary CarE Reduction of Blood Pressure Study (VIPER-BP) Study is an open-label, randomised controlled trial comparing usual primary care management with an intensive BP management strategy using three forms of valsartan-based therapy (mono-therapy, thiazide diuretic or calcium channel blocker combinations) to achieve individualised BP control.

Methods

To identify the features of General Practitioner (GP) management of hypertension in Australia, we analyse the response to a case scenario-based survey of 500 GPs. We subsequently recruited a national cohort of GP Investigators to enrol up to 2500 patients into the VIPER-BP Study.

Results

GP responses clearly demonstrated that, compared to the VIPER-BP intervention, a heterogeneous approach to the primary care management of hypertension persists in Australia. By November 2010, 2157 hypertensive patients from 272 actively recruiting GP Investigators were enrolled into the study. Of these, 1965 (91%) patients were entered into a standardised “run-in” phase of 28 days of valsartan 80 mg/day. Subsequently, 1285 patients were randomised to usual care (n = 435) or the VIPER-BP intervention (n = 850). There was a predominance of males (62%), whilst 55% had pre-existing diabetes or cardiovascular disease and 63% had been previously treated for hypertension. Mean systolic and diastolic BP on randomisation for men and women, respectively, was 148 ± 15/88 ± 11 and 148 ± 18/87 ± 10 mm Hg.

Conclusions

In contrast to typical primary care management of hypertension, VIPER-BP combines more intensive and aggressive therapies with structured management to more rapidly attain and sustain individualised BP targets in hypertensive patients.     

Aortic valve sparing in 120 patients with aortic root aneurysms

Introduction and objectives

Several aortic valve sparing techniques have been described for the treatment of aortic root aneurysms. We report our experience using the reimplantation technique in 120 patients.

Methods

Between March 2004 and October 2010, 120 patients with aortic root aneurysms underwent David operations. Of these, 51 were diagnosed with Marfan syndrome. Mean patient age was 31 ± 12 years. The mean diameter of the sinuses of Valsalva was 51 ± 5 mm and moderate/severe aortic regurgitation was present in 16% of these patients. In the other 69 patients mean age was 56 ± 14 years, the mean diameter of the sinuses of Valsalva was 53 ± 7 mm and moderate/severe aortic regurgitation was present in 66%. A bicuspid aortic valve was presented in 14 cases.

Results

Hospital mortality was 1.7%. Mean follow-up was 37 ± 21 months; 94% of the patients survived and 96% had an aortic regurgitation below grade II during 5 years of follow-up. One patient required re-operation because of severe aortic regurgitation. No endocarditis or thromboembolic complications have been documented, and 96% of the patients did not receive any anticoagulation therapy.

Conclusions

Short- and mid-term results with the reimplantation technique for aortic root aneurysms are excellent. This technique prevents the need for chronic anticoagulation treatment as well as the complications arising from mechanical prostheses, and it should be the treatment of choice for young patients.Full English text available from: www.revespcardiol.org     

Histological regression of liver fibrosis with immunosuppressive therapy in autoimmune hepatitis

Reversibility of liver fibrosis with immunosuppressive therapy (IT) has been described in autoimmune hepatitis (AIH)

Objective

To compare initial fibrosis and fibrosis after IT in patients with AIH.

Methods

A total of 54 patients were admitted with positive ANA or AML antibodies, or both, elevated IgG immunoglobulins and who met international criteria for a diagnosis of AIH. The mean age was 39 years (range 13-65) and there were 47 women (87%). Two liver biopsies were taken: one at diagnosis and another at a mean of 28 ± 8 months after initiation of IT with prednisone and azathioprine. The degree of inflammation (0-18) and fibrosis (0-6) according to Ishak score was compared between the initial and the follow-up biopsy.

Results

Fibrosis decreased from 2.9 ± 0.3 to 2.2 ± 0.3 (p = 0.005) and histological activity index from 6.8 ± 0.45 to 2.6 ± 0.2 (P < .001). In subgroups, fibrosis decreased from 3.6 ± 0.4 to 1.4 ± 0.3 (P < .001) in 22 patients (41%), was unchanged in 27 (50%) and increased in five (9%). There were seven patients with histological cirrhosis at IT initiation. After IT, four showed a reduction in Ishak score (achieving scores of 0-3). Transaminase values were not associated with histological improvement.

Conclusion

Fibrosis in patients with AIH significantly improved with IT, emphasizing the importance of studying the prognostic factors associated with this favorable response.