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.

Diabetes in postmenopause: different influence on bone mass according to age and disease duration.

OBJECTIVE: Studies addressing the influence of diabetes mellitus on bone metabolism have yielded conflicting results. The aim of the present study is to investigate the bone mineral density (BMD) status of postmenopausal diabetic women with different ages or diabetes duration. METHODS: Two hundred postmenopausal women with type 2 diabetes (DM) and 800 postmenopausal healthy women (PMP), serving as control subjects, were studied. Subjects were divided into either 6 groups according to 5 year age segments, or 6 groups according to 5 year segments of diabetes duration. BMD was measured at the femoral neck and at the trochanter major with dual energy X-ray absorptiometry. RESULTS: Diabetic women studied as a whole, exhibited significantly higher BMD values compared to healthy postmenopausal women at both femoral neck and trochanter. Diabetic women of 48-53, 53-58, 58-63 and 63-68 age groups had significantly higher BMD values than the respective control groups, whereas BMD values of DM 73-78 were significantly lower compared to the PMP 73-78 group at both anatomic sites. When the same diabetic women were divided according to diabetes duration (DUR), groups DUR 6-10 and DUR 11-15 exhibited significantly higher BMD values at both anatomic sites compared to control groups. In contrast, BMD values of group DUR 21-25 were significantly lower only at the femoral neck. CONCLUSIONS: Type 2 diabetes mellitus' influence on bone metabolism seems to depend on the patient's disease duration and age. The initial positive effect on bone mass appears to be ameliorated as age or disease duration advance. Studies concerning type 2 diabetes and bone mass should take these parameters into account.

Bone mineral density of both genders in Type 1 diabetes according to bone composition.

AIMS: This study is an investigation of the impact of Type 1 diabetes on bone mineral density (BMD) with regard to bone composition. MATERIAL AND METHODS: Thirty male and 30 premenopausal female patients with Type 1 diabetes (IDD) were retrospectively compared with an equal number of healthy individuals, matched on a person-to-person basis and to the reference population mean. BMD was measured at the L2-L4 vertebrae and femoral neck (FN) by dual energy X-ray absorptiometry (DXA). RESULTS: BMD absolute values were significantly lower in the diabetic than in the healthy males at vertebrae and FN (P<.05). The vertebral BMD values of diabetic women did not significantly differ, whereas those of FN were significantly lower compared with those of the healthy participants. FN age-adjusted BMD values (Z scores) were significantly lower than those of the healthy persons and the population reference mean in both genders (P=.01, <.001 for males and <.01 for females), whereas regarding the vertebrae, only in the diabetic males (P<.05 and <.01 respectively). The percentages of osteopenia and osteoporosis were significantly higher in the male compared to the female diabetic patients (P<.001). No significant correlations existed between the BMD values and diabetes duration, glycosylated hemoglobin (HbA1c) concentration, or age of diabetes onset. Similar results were obtained when applying stepwise multiple regression analysis to explain the BMD value variance. CONCLUSIONS: Young males with Type 1 diabetes exhibit significantly lower BMD values of trabecular and mixed cortical-trabecular bone, compared with matched healthy persons. Premenopausal females with Type 1 diabetes present significantly lower BMD values of mixed bone only. Blood glucose control and diabetes duration do not appear to influence BMD behavior.

Discrepancies between vertebral bone density values: the least dense vertebra.

Vertebral bone mineral density (BMD) measurements by DXA are considered reliable indicators of local fracture risk in the absence of radiographic deformities. The clinical evaluation of one individual vertebra presenting a BMD value significantly less than the others is attempted in this study. For a period of 30 months, BMD measurements of L1-L4 vertebrae and femoral neck (FN) were performed by DXA in 817 postmenopausal women, aged under 65 years, with a BMI less than 33 kg/m(2). In 204 (25%) of these women (group A), the least dense vertebra (LDV) presented a BMD value lower than 92.4% from the immediate denser vertebra. The remaining 613 women comprised group B. Women with X-ray proven vertebral degenerative lesions or deformities were excluded from the study. Among the four measured vertebrae, L1 was the most frequent LDV (47%), whilst L3 was the most rare (2%). Absolute and age-adjusted BMD values of L1-L4 and FN, as well as the proportions of osteopenic or osteoporotic women, did not differ significantly between the two groups. A significant positive correlation was observed between either L1-L4 or LDV and FN BMD values in both groups, but stepwise multiple regression analysis revealed that in group A the LDV did not participate in the model explaining the variability of the FN BMD values. In group B, the least dense vertebra was the only variable participating in the respective model (adjusted-R(2) = 37.7%). It is concluded that in a significant proportion of relatively young postmenopausal women, a wide variance of BMD values exists between individual vertebral BMD values without radiographic background. L1 was the most frequent LDV and L3 the most rare. In such cases, the evaluation of the least dense vertebra seems to offer an alternative estimation of vertebral bone mass, instead of mean L1-L4.

Diabetes and premature menopause: is their co-existence detrimental to the skeleton?

OBJECTIVE: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial. DESIGN AND METHODS: BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years. RESULTS: Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women. CONCLUSIONS: Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.

Does subclinical hypercortisolism adversely affect the bone mineral density of patients with adrenal incidentalomas?

OBJECTIVE: Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of > 70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS: Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72). CONCLUSIONS: In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.

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.

The type and time of menopause as decisive factors for bone mass changes.

BACKGROUND: Early menopause, whether it be natural or surgical, is one of the established risk factors for osteoporosis. Surgical menopause, however, differs from natural menopause owing to the abrupt cessation of estrogen secretion. This study attempts to investigate the influence of menopause type on bone mineral density (BMD) changes. METHODS: Four groups, each consisting of 30 women, were compared: early menopause (EMP), surgical menopause (SUMP) and two groups of natural menopause. The two groups share a similar number of years since menopause (YSM) but have a different chronological age (NMPO), or share a similar age but different YSM (NMPY) to the EMP and SUMP. BMD was measured by the DXA method at L2-L4 vertebrae and proximal femur. RESULTS: Mean vertebral BMD of EMP was lower than that of SUMP (P < 0.05) and of NMPY (P < 0.001) women. Femoral neck BMD did not differ between SUMP and EMP women but both exhibited significantly lower BMD than either natural menopause groups. BMD of SUMP and vertebral BMD of NMPY women was inversely correlated to chronological age and to number of YSM. Pertaining to T-score values according to the osteoporotic range, NMPO, EMP and SUMP women being homogeneous exhibited significantly lower values than NMPY in the vertebrae (F-ratio = 7.84, P < 0.001). Whereas, in the femoral neck and the trochanter major, EMP and SUMP categories presented significantly lower T-score values than the NMPO and NMPY (F = 3.61, P < 0.01 and 2.8, P < 0.05 respectively). CONCLUSION: Women with early menopause exhibit lower vertebral BMD than women of similar age after either surgical or natural menopause. In women of similar age, surgical menopause results in lower vertebral and femoral neck densities compared to natural menopause. Chronological age and the interval after menopause negatively affects bone density in women with similar age whether in surgical or natural menopause.