Metabolic syndrome and prediabetes identify overlapping but not identical populations.

OBJECTIVE: The metabolic syndrome (MetS) is a cluster of risk factors related to cardiovascular disease. Prediabetes, identified by impaired fasting glucose and/or impaired glucose tolerance, may predict future development of diabetes mellitus. However, it is not clear whether MetS and prediabetes represent the same or different clinical entities. This study compares MetS and prediabetes in terms of cardiovascular risk factors and target organ damage. RESEARCH DESIGN AND METHODS: A total of 524 overweight and obese (body mass index, BMI >or= 27 kg/m (2)) adults, mean age 53.6 +/- 10.3 years, 264 men and 260 women, were studied. All participants underwent a thorough clinical and laboratory evaluation, including an oral glucose tolerance test and insulin measurements. Echocardiography, carotid ultrasonography, and pulse wave analysis were also performed for the detection of target organ damage. NCEP-ATP III and ADA criteria were used for the diagnosis of MetS and prediabetes. RESULTS: The prevalence of MetS and prediabetes was 38.7 and 25.4 %, respectively. Overall, 129 individuals (24.6 %) had MetS without prediabetes (group M) and another 59 (11.3 %) prediabetes without MetS (group P). Group P had decreased albumin excretion (p = 0.033) and more thickened common carotid intima-media in comparison to group M (p = 0.032). Furthermore, group M was associated with higher C-reactive protein levels. Multiple logistic regression analysis revealed that advanced age (p < 0.0001, OR 1.11, 95 % CI 1.06 - 1.16), low insulin secretion (p < 0.0001, OR 0.05, 95 % CI 0.02 - 0.18 for insulinogenic index), and increased insulin resistance (p = 0.0003, OR 3.22, 95 % CI 1.71 - 6.07 for HOMA-IR) were associated with group P. CONCLUSIONS: Our data demonstrate that MetS and prediabetes have an overlapping pattern. MetS appears to have a more pronounced effect on early renal dysfunction and increased inflammatory activation, while prediabetes tends to be associated with early carotid structural changes. These findings may be due to a different pathophysiologic substrate of these clinical phenotypes in terms of insulin resistance and secretion, as well as to the varying prevalence of cardiovascular risk factors.

High-dose monotherapy vs low-dose combination therapy of calcium channel blockers and angiotensin receptor blockers in mild to moderate hypertension.

The objectives of the study were to compare long-acting dihydropyridine calcium channel blockers (CCBs) with angiotensin II receptor blockers (ARBs) according to the ambulatory blood pressure monitoring (ABPM) profile in stage 1 and 2 newly diagnosed hypertensives and also to evaluate the efficacy of high-dose monotherapy vs low-dose combination therapy of the two drug categories among the subjects with inadequate blood pressure (BP) control after conventional low-dose monotherapy. We obtained 24-h ABPM readings from 302 subjects with newly diagnosed stage 1 or 2 essential hypertension. The study protocol consisted of initial drug treatment with a low dose of either CCBs or ARBs. Hypertensives who did not achieve BP control were randomized to high-dose monotherapy of either category of drug or low-dose combination therapy. CCBs and ARBs in low-dose monotherapy achieved BP control in 53.8 and 55.3% of the cases, respectively. However, subjects under treatment with CCBs experienced side effects more often and required that treatment be discontinued. Hypertensives who failed to control their BP with low-dose monotherapy did significantly better with low-dose combination treatment (61.6%) than with high-dose CCBs (42.8%) or ARBs (40.5%) monotherapy (P<0.05). In terms of ABPM, low-dose combination therapy exhibited better 24-h BP profile according to trough-to-peak ratio, hypertensive burden and BP variability. In conclusion, low-dose ARBs and CCBs have a comparable effect in subjects with grade 1 and 2 arterial hypertension. In hypertensives who are not controlled by low-dose monotherapy, low-dose combination therapy proves be more efficacious than high-dose monotherapy.

HLA phenotypes as promoters of cardiovascular remodelling in subjects with arterial hypertension.

The objective of this study was to investigate the association between human leukocyte antigens (HLA) phenotypes and cardiovascular remodelling, as expressed by left ventricular mass (LVM) and carotid intima-media thickness (IMT), in hypertensives. We examined 153 subjects with arterial hypertension and 61 normotensive controls living in the greater Athens area. The population was classified into three groups and specifically group I (normotensives), group II with Grade 1 hypertension and group III with Grade 2 or 3 hypertension. HLA class I and class II antigens were studied by microlymphocytotoxic technique. Carotid IMT and LVM were determined by ultrasonography. The prevalence of HLA DQ7 in the hypertensive cohort was 27.4% that was significantly smaller than the 52.5% among the controls (P = 0.002). The HLA DR11 was found in 24.0% of the hypertensives and in 52.5% of the controls (P < 0.001). Group III hypertensives with HLA DR11 exhibited significantly higher LVM/h in comparison to the hypertensives without this HLA (199.0 +/- 28.8 vs 171.2+44.1g/m, P = 0.009). This association was not present in groups I and II. Similarly, group III hypertensives with HLA DQ7 were characterized by higher IMT in comparison to those without this HLA (0.94 +/- 0.19 vs 0.83 +/- 0.23 mm, P = 0.048). HLA DR17 was associated with higher IMT in both groups II and III (1.00 +/- 0.19 vs 0.82 +/- 0.19 mm, P = 0.046 and 1.01 +/- 0.23 vs 0.84 +/- 0.22 mm, P = 0.049, respectively) but not in group I. In conclusion, certain HLA phenotypes may be related to the levels of arterial blood pressure. Moreover, it seems that these HLA phenotypes may identify subjects with arterial hypertension that are more prone to develop cardiovascular hypertrophy.

Intermittent claudication unmasking underlying Fabry's disease.

In a 53-year-old woman, admitted to our Department with leg pain, peripheral arterial occlusive disease (PAOD) was diagnosed. The absence of cardiovascular risk factors in this middle-aged woman, the unexplained burning pain during both effort and rest of the lower extremities mimicking severe ischemia, decreased sweating and cold induced Raynaud's phenomenon raised the suspicion of an underlying predisposing disease. The coexistence of painful acroparesthesias, angiokeratomas, left ventricular hypertrophy (LVH), corneal opacities and lenticular lesions suggested the diagnosis of Fabry's disease, which was confirmed by low serum levels of a-galactosidase-A activity. This case, presented with intermittent claudication due to generalized atherosclerosis, is quite unusual, since Fabry's disease rarely produces symptoms in female carriers.

Association of the HLA antigens with early atheromatosis in subjects with type 2 diabetes mellitus.

BACKGROUND: Inflammation plays an important role in the pathogenesis of atherosclerosis. The major histocompatibility complex, as expressed by the human leukocyte antigens (HLA) is considered to regulate the immune response. The aim of this study was to investigate the association of the HLA antigens with vascular remodeling estimated by the carotid intima-media thickness (IMT) in subjects with type 2 diabetes mellitus (DM). METHODS: We evaluated 197 patients with type 2 DM, 80 males and 117 females, mean age 61.8+/-7.8 years, with no history of cardiovascular events. The presence of other major cardiovascular risk factors was recorded. The currently identified HLA class I (-A, -B, -Cw) and class II (DR, -DQ) antigens were studied by a classical 2 step microlymphocytotoxic technique in peripheral blood T and B lymphocytes. Measurements of the IMT were performed in the right and left common carotid arteries, 15-20 mm proximal to the dilatation of the carotid bulb in an end-diastolic "frozen" and magnified B-mode ultrasonographic image. Glycosylated hemoglobin A1c (HbA1c) and C-reactive protein (CRP) were also measured. The results are presented as mean +/-1 standard deviation. RESULTS: Regarding the HLA phenotypes in the final analysis we tested a total of 24 HLA antigens that exhibited a frequency of at least 5% in our diabetic population. Only HLA A3 was found to be significantly associated with the carotid IMT. Forty-nine (24.9%) diabetics were HLA A3 positive (group A), while 148 (75.1%) were HLA A3 negative (group B) and had mean IMT of 0.89+/-0.16 mm and 0.98+/-0.21 mm, respectively (p<0.01). Also the two groups differed significantly in respect to CRP, with group A exhibiting lower serum levels (1.1+/-0.4 mg/dl vs 2.6+/-0.7 mg/dl for group A and B, respectively, p<0.05). However, no differences were observed between the two groups as far as blood glucose control, arterial hypertension and dyslipidaemia were concerned. CONCLUSIONS: Human leukocyte antigen A3 is associated with less vascular damage, as expressed by carotid wall thickness, in subjects with type 2 DM. These subjects may be characterized by a milder inflammatory response, as shown by the lower serum levels of CRP.

Association of specific HLA phenotypes with left ventricular mass and carotid intima-media thickness in hypertensives.

The aim of this study was to investigate the hypothesis that the expression of certain HLA antigens may constitute a risk marker for cardiovascular hypertrophy in subjects with arterial hypertension. We examined 158 subjects with newly diagnosed arterial hypertension. HLA class I (-A, -B, -Cw) and class II (-DR, -DQ) antigens were studied by two-step microlymphocytotoxic technique in peripheral T and B lymphocytes. Carotid intima-media thickness (IMT) was determined noninvasively by ultrasonography. The left ventricular mass was calculated according to the formula of Devereux and was normalized by the individual's height (LVM/h). The individuals with DR13 and DR17 were characterized by higher values of IMT compared to those without these HLA (0.096+/-0.018 cm v 0.085+/-0.021 cm, P = .011, 0.100+/-0.019 cm v 0.084+/-0.021 cm, P = .012, respectively). The presence of HLA DQ7 was characterized by markedly higher values of IMT that just failed to reach statistical significance (0.091+/-0.019 cm v 0.084+/-0.022 cm, P = .045). Furthermore, subjects with HLA DQ7 and DR11 exhibited higher values of LVM/h in comparison to those without these HLA (191.3+/-36.2 g/m v 166.9+/-41.0 g/m, P = .029 and 194.6+/-34.3 g/m v 166.6+/-40.9 g/m, P = .034, respectively). Hypertensive subjects with HLA B51 tended to have lower LVM/h (166.6+/-39.0 g/m with v 176.0+/-41.7 g/m without HLA B51, P = .045). In conclusion, it can be postulated that certain HLA phenotypes exhibit an association with increased carotid IMT and left ventricular mass in hypertensive subjects. The determination of these antigens may help to identify subjects at high risk for cardiovascular events.

Distribution of different HLA antigens in Greek hypertensives according to the angiotensin-converting enzyme genotype.

The angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is an independent risk factor for cardiovascular disease. It has also been suggested that some HLA genes may contribute to the genetic susceptibility to essential hypertension. So far, an association between ACE polymorphism and HLA antigens in arterial hypertension has not been reported. We have studied 94 subjects with newly diagnosed essential hypertension, 49 men and 45 women (mean age, 52.3 +/- 11.3 years), as well as 104 randomly selected, age- and gender-matched normotensive individuals (54 men and 50 women, mean age 48.7 +/- 10.8 years). Both cohorts originated from the Greek population and lived in the greater Athens area. The ACE genotype was analyzed by polymerase chain reaction. HLA class I and II antigens were studied by serologic and molecular techniques. The prevalence of the ACE genotypes did not differ significantly between hypertensives and normal individuals. The casual blood pressure levels and the average ambulatory blood pressure levels were similar among the three ACE genotypes. Hypertensives with the ACE-DD genotype were characterized by an increased prevalence of the HLA-A2 antigen (50% v 31.4%, P < .005) and DR6 (16.7% v 11.4%, P < .01) in comparison to the normotensive subjects with the ACE-DD genotype. HLA-A24 was found more frequently among the hypertensives with the ACE-ID genotype than in the normal controls with the same genotype (35.5% v 26.4%, P < .05). ACE-DD genotype is associated with a high prevalence of specific HLA antigens. The coexistence of the ACE-DD genotype with certain HLA phenotypes could reveal a distinct hypertensive population with increased risk for cardiovascular events.

Implantable cardioverter defibrillator-an unusual case of inappropriate discharge during showering.

The evolution of diagnostic information provided in implantable cardioverter defibrillators (ICDs) has paralleled the advances in the therapeutic options incorporated in these systems. Contemporary devices are capable of providing recordings of electrical events surrounding all delivered and aborted device therapy. This report presents un unusual case of inappropriate discharge of an ICD, resulting from electromagnetic interference. A transvenous ICD system (Sentry Hot Can 4310 HC, Telectronics Denver, CO), was implanted in a patient with ischemic heart disease due to episodes of ventricular tachycardia refractory to antiarrhythmic treatment. One month post-implant the patient reported two consecutive shocks from the device while showering. The non-physiological cycle length (100 ms) recorded in conjunction to the scenario of the event, raised the suspicion of electromagnetic interference through electrical current leakage in the bathroom, an hypothesis that was subsequently proved. This case report underscores that electromagnetic interference can become hazardous in common daily activities of patients with an ICD.

Ventricular performance and quality of life in patients who underwent radiofrequency AV junction ablation and permanent pacemaker implantation due to medically refractory atrial tachyarrhythmias.

UNLABELLED: In patients with drug refractory atrial tachyarrhythmias and previous failed attempts of ablation of the arrhythmia substrate, radiofrequency (RF) modulation or ablation of the atrioventricular (AV) junction is an alternative procedure. AIM: Of this study was to assess the efficacy and long term results of RF AV junction ablation in conjunction with permanent pacemaker implantation, in the management of patients with drug resistant atrial tachyarrhythmias. METHODS: Between 4/92 and 1/97, 46 patients (30 male, 16 female, 67 +/- 12 years) underwent RF AV junction ablation because of paroxysmal atrial fibrillation (24 patients), chronic atrial fibrillation (13 patients), atrial flutter (5 patients) and atrial tachycardia (4 patients). The underlying heart disease was dilated cardiomyopathy (16), ischemic heart disease (9), hypertensive heart disease (6), hypertrophic cardiomyopathy (3), atrial septal defect (2) and non structural heart disease (10). The duration of symptoms was 6.4 +/- 3.5 years at a maximal heart rate 169 +/- 24 bpm. The hospital admissions in the last 12 months were 8.2 +/- 3 per patient. The failed antiarrhythmic drugs were 3.5 +/- 2.1. The functional NYHA class was 2.7 +/- 0.6. Patients with atrial flutter and atrial tachycardia had previous failed attempts of RF ablation of the arrhythmia substrate. Thirty patients had a compromised left ventricular systolic function with LVEF below 50% (mean 34 +/- 9%). AV junction ablation was achieved in all patients after 4 +/- 2.5 RF applications. Post ablation, the selected pacing mode was DDD-R for the 33 patients with paroxysmal atrial tachyarrhythmias and VVI-R for the 13 pts with chronic atrial fibrillation. The dual chamber pacemakers implanted had the option of automatic mode switch. RESULTS: During the follow-up period of 28 +/- 13 months (6-47), AV conduction recovered in 1 patient. Antiarrhythmic treatment was necessary in only 7 patients. Post ablation the new functional NYHA class was 1.4 +/- 0.8 (p < 0.001). Post ablation hospital admissions, including ordinary pacemaker follow-up visits, were 4 +/- 1 per patient per year (p < 0.001). Six months after the procedure the LVEF of the study population was increased from 42 +/- 16% to 50 +/- 14% (p = NS). In the 30 patients with heart failure the LVEF was significantly increased to 46 +/- 8% (p < 0.05). Symptomatic relief or significant improvement was observed in all patients as showed by the answers given in a customized questionnaire before and after the procedure. CONCLUSIONS: In patients with drug refractory atrial tachyarrhythmias, RF AV junction ablation and permanent pacemaker implantation is an alternative therapy with excellent long term results in terms of arrhythmia control, ventricular performance and quality of life.