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.

Early vascular lesions in subjects with metabolic syndrome and prediabetes.

AIM: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, while prediabetes, identified by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), predicts future development of diabetes mellitus. Although MetS and prediabetes have a strong interrelation, it is unclear whether they denote the same risk for cardiovascular complications. The aim of the study was to compare overweight and obese individuals with MetS and prediabetes in terms of early carotid artery atheromatosis and renal dysfunction. METHODS: A total of 524 overweight and obese (body mass index, BMI = or >27 kg/m2) adults, mean age 56.7+/-11.8 years, 264 men and 260 women, were studied. All participants underwent a thorough clinical and laboratory evaluation, including an oral glucose tolerance test. Carotid artery ultrasonography was performed and 24 h urine albumin excretion was measured. NCEP-ATP III and ADA criteria were used for the diagnosis of MetS and prediabetes. RESULTS: Overall, 129 individuals (24.6%) had MetS without prediabetes and another 59 (11.3%) prediabetes without MetS. Individuals with prediabetes had lower albumin excretion (P=0.033) and more thickened common carotid intima-media in comparison to those with MetS (P=0.032). Furthermore, MetS was associated with higher C-reactive protein levels in comparison to prediabetes (P=0.05). CONCLUSIONS: The MetS seems to have a more pronounced impact on early renal dysfunction than prediabetes, while the latter to early carotid artery structural changes.

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.

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.

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.

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.

The effect of aliskiren versus ramipril-based treatment on the Ambulatory Arterial Stiffness Index in hypertensive patients.

AIM: Aim of the present study was to compare the effectiveness of two renin-angiotensin-aldosterone system inhibitors in arterial stiffness reduction in previously untreated hypertensive patients. METHODS: In this open label study, 154 naïve, or not treated in the last six months hypertensive patients were randomly assigned to receive aliskiren 300 mg or ramipril 5 mg daily. Six weeks after the initiation of treatment, patients were evaluated for blood pressure (BP) control. Patients with SBP ≥140 and/or DBP ≥90 mmHg were assigned to an adjunct of 25 mg hydrochlorothiazide as combination treatment. A re-evaluation of BP control was done after another 6 weeks. Individuals with BP ≥140/90 mmHg were further administered amlodipine 5 mg. The final evaluation was performed six months after the start of the study. Twenty four-hour ambulatory blood pressure monitoring was carried out and the ambulatory arterial stiffness index (AASI) was calculated at baseline and after 6 months of treatment. RESULTS: Aliskiren-based therapy, as compared with ramipril-based therapy reduced BP to a similar degree: 13±11 vs. 12±11 mmHg reduction in systolic (P=0.34) and 8±7 vs. 7±7 mmHg reduction in diastolic BP (P=0.44). AASI was reduced by 0.04±0.1 in the aliskiren group and by 0.02±0.2 in the ramipril group. AASI reduction did not differ significantly in the two groups (P=0.13). CONCLUSION: In hypertensive patients, aliskiren-based treatment as well as ramipril-based treatment appears to have a beneficial effect on arterial stiffness. As arterial stiffness is an important modifiable risk factor, our findings highlight the value of aliskiren beyond BP lowering properties.

Differential impact of angiotensin receptor blockers and calcium channel blockers on arterial stiffness.

AIM: Arterial stiffness, assessed by ambulatory arterial stiffness index (AASI), is an independent predictor of cardiovascular disease (CVD) mortality in hypertensives. However, it is unclear whether certain antihypertensive drugs are conducive to the reduction in CVD morbidity and mortality through their beneficial effect on arterial stiffness. Therefore, we compared the effect of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on AASI in a hypertensive population. METHODS: We studied 188 individuals with newly-diagnosed essential hypertension without organ damage or CVD. AASI was calculated from twenty-four-hour ambulatory blood pressure monitoring (ABPM) readings at baseline and after twelve weeks of antihypertensive treatment. Therapy was initiated with a low-dose of CCB (group A) or ARB (group B). After six weeks, subjects with poor office blood pressure (BP) control were further randomized to high-dose monotherapy (CCB in group C or ARB in group D) or low-dose combination therapy (CCB plus ARB, group E). RESULTS: Groups A and B showed similar reductions in systolic and diastolic BP (r=-0.12, P=0.92 and r=-0.07, P=0.58 in group A and r=-0.06, P=0.67 and r=-0.04, P=0.73 in group B, respectively). However, only subjects in group B achieved significant AASI decrease (P<0.001). Similarly, subjects in groups C, D and E also displayed a comparable BP reduction, but only those in group E attained significant AASI decrease (P=0.001). CONCLUSION: ARB treatment, either as low-dose monotherapy or in combination with a CCB in hypertensives who do not achieve BP control with monotherapy, has a beneficial effect on arterial stiffness. As arterial stiffness is an important modifiable risk factor, our findings highlight the value of ARBs beyond their BP lowering properties.

The effect of metformin on the incidence of type 2 diabetes mellitus and cardiovascular disease risk factors in overweight and obese subjects--the Carmos study.

UNLABELLED: We investigated whether the addition of metformin to the treatment of overweight and obese individuals further reduces the incidence of type 2 diabetes mellitus (T (2)DM), prediabetes and metabolic syndrome (MetS) and improves cardiovascular disease (CVD) risk factors (RFs). DESIGN AND METHODS: We studied 366 adults (mean age 53.0+/-0.5 SE years, and mean BMI 32.3+/-0.2 SE Kg/m (2)) without CVD. All subjects received lifestyle recommendations and drug management of CVD-RFs, whilst 95 of them were additionally given metformin. The follow-up period lasted 12 months. RESULTS: At the end of the study the frequency of T (2)DM in the metformin and non-metformin group was 1.1 and 8.1%, respectively (risk difference=-7% with 95% CI from -12.7% to -1.4%, p=0.012). Participants with prediabetes displayed a greater reduction in the incidence of T (2)DM after taking metformin compared to those who had not received this drug (risk difference=-18.5% with 95%CI from -33.1% to -3.9%, p=0.010). Metformin had a similar beneficial impact on subjects with MetS (risk difference=-12.9% with 95% from -25% to -0.7%, p=0.040) and this was attributed to the greater increase in HDL-C (p=0.046) and decrease in fasting plasma glucose levels (p=0.024). Metformin also achieved a greater reduction in total cholesterol and LDL-C levels (metformin vs. non-metformin treated subjects: -31.9 vs. -17.3 mg/dl, p=0.001, and -26.2 vs. -15.9 mg/dl, p=0.006, respectively). CONCLUSIONS: Metformin reduces the occurrence of T (2)DM in overweight and obese non-diabetic adults and decreases the rate of MetS by improving the CVD risk factor profile.