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Biomedical subjects

Gaetano Vaudo

Publications and source records attributed to Gaetano Vaudo.

At least 19 recordsLinked to original sources

Age-specific relationship of aortic pulse wave velocity with left ventricular geometry and function in hypertension.

Aortic pulse wave velocity (PWV), generally considered an intrinsic marker of arterial stiffness, might depend in part on the velocity of myocardial fiber shortening, but the relation between PWV and myocardial function in humans has been understudied. A total of 237 untreated hypertensive subjects over a wide age range (18 to 88 years) underwent aortic PWV determination and echocardiography, from which the mean velocity of circumferential fiber shortening was calculated as a measure of the velocity of myocardial shortening, and relative wall thickness was taken as a measure of left ventricular concentric remodeling. Patients were divided in 3 age groups (<40 years, 40 to 59 years, and >or=60 years). In the young, aortic PWV was directly associated with heart rate-corrected velocity of circumferential fiber shortening (r=0.39; P=0.002) but not to relative wall thickness (r=-0.01; P=0.95). The opposite was found in the older group, in which aortic PWV was accompanied by a concentric left ventricular geometric pattern (r=0.44 with relative wall thickness; P=0.009) and a reduced velocity of circumferential fiber shortening (r=-0.54; P<0.001) and stress-corrected midwall fractional shortening (r=-0.56; P<0.001). Intermediate values were found in the middle-aged group (r=0.23; P<0.01 with relative wall thickness; r=-0.07, P value not significant with velocity of circumferential fiber shortening). In conclusion, the relation between aortic PVW and the left ventricle is strongly age dependent. These data suggest that, in young people, aortic PWV is partly determined by an increased velocity of myocardial shortening. With increasing age, a relationship between aortic PWV (as a measure of arterial stiffness) and left ventricular concentric geometry emerges, which ultimately leads to a depressed ventricular systolic function.

Adult↗

Effects of rosuvastatin on 3-nitrotyrosine and aortic stiffness in hypercholesterolemia.

BACKGROUND AND AIMS: Early atherosclerosis is characterized by reduced large artery distensibility, paralleled by an increased peroxynitrite formation and nitration of tyrosine in proteins. The aim of the present study was to investigate the short-term effect of cholesterol lowering with rosuvastatin on 3-nitrotyrosine (3-NT), a marker of peroxynitrite-mediated oxidative stress, and on arterial stiffness. METHODS AND RESULTS: 71 outpatients with primary hypercholesterolemia were recruited for this randomized open-label intervention study; 35 patients were assigned to 4-week rosuvastatin therapy (10mg daily) with a low-fat diet, and 36 patients to a low-fat diet only. Within the cohort of 71 hypercholesterolemic patients, there was a significant correlation between cholesterol levels, 3-NT and aortic pulse wave velocity (aPWV), that is a reliable measure of aortic stiffness. Among those patients who received rosuvastatin, significant reductions in plasma cholesterol, 3-NT and aPWV were observed. Reductions in both aPWV and 3-NT levels correlated significantly with the decrease in plasma cholesterol. Reduction of plasma cholesterol was the only independent predictor for reduced arterial stiffness following rosuvastatin therapy. CONCLUSION: Cholesterol reduction achieved following short-term rosuvastatin therapy is associated with a decrease in peroxynitrite-mediated oxidative stress and an improvement in large artery distensibility; reduction in arterial stiffness is directly attributable to rosuvastatin-induced cholesterol lowering and not to reduction of plasma 3-NT levels.

Adult↗

Racial difference in endothelial function: role of the infective burden.

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.

Adult↗

Different impact of the metabolic syndrome on left ventricular structure and function in hypertensive men and women.

Metabolic syndrome (MS) is increasingly recognized as an important cardiovascular risk factor in hypertension, but its influence on left ventricular (LV) mass and function in the 2 genders has not been specifically addressed. Among 618 nondiabetic, untreated hypertensive subjects, echocardiographically detected LV mass was significantly greater in subjects with MS. A significant interaction was observed between sex and the MS (P<0.003 for the multiplicative interaction term). Compared with women without the MS, those with the syndrome had a 24% greater LV mass (49.5+/-12 versus 40.0+/-10 g x m(-2.7); P<0.001), whereas the difference was only 9% in men (50.3+/-12 versus 46.1+/-10 g x m(-2.7); P=0.003). A greater prevalence of LV hypertrophy was found in women (37% versus 14%; P<0.001) but not in men (39% versus 29%; P=0.09) with the MS. After adjustment for the effect of age, body mass index, 24-hour systolic blood pressure, and several confounders, the MS was independently associated with a greater LV mass index in women (regression coefficient, 4.80; P<0.001) but not in men. Women with the MS also had a greater LV relative wall thickness (0.42+/-0.07 versus 0.39+/-0.07; P=0.004) and a depressed afterload-corrected midwall fractional shortening (94.0+/-12% versus 101.0+/-13%; P<0.001) than women without the syndrome, whereas no differences emerged in men. We conclude that, in untreated hypertension, MS has a different impact on LV hypertrophy and function in men and women. The effect of MS is more pronounced in women and is partly independent from the effect of several hemodynamic and nonhemodynamic determinants of LV mass.

Adult↗

The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families.

OBJECTIVE: To better understand the role of lecithin:cholesterol acyltransferase (LCAT) in lipoprotein metabolism through the genetic and biochemical characterization of families carrying mutations in the LCAT gene. METHODS AND RESULTS: Thirteen families carrying 17 different mutations in the LCAT gene were identified by Lipid Clinics and Departments of Nephrology throughout Italy. DNA analysis of 82 family members identified 15 carriers of 2 mutant LCAT alleles, 11 with familial LCAT deficiency (FLD) and 4 with fish-eye disease (FED). Forty-four individuals carried 1 mutant LCAT allele, and 23 had a normal genotype. Plasma unesterified cholesterol, unesterified/total cholesterol ratio, triglycerides, very-low-density lipoprotein cholesterol, and pre-beta high-density lipoprotein (LDL) were elevated, and high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II, cholesterol esterification rate, LCAT activity and concentration, and LDL and HDL3 particle size were reduced in a gene-dose-dependent manner in carriers of mutant LCAT alleles. No differences were found in the lipid/lipoprotein profile of FLD and FED cases, except for higher plasma unesterified cholesterol and unesterified/total cholesterol ratio in the former. CONCLUSIONS: In a large series of subjects carrying mutations in the LCAT gene, the inheritance of a mutated LCAT genotype causes a gene-dose-dependent alteration in the plasma lipid/lipoprotein profile, which is remarkably similar between subjects classified as FLD or FED.

Adult↗

Metabolic syndrome is associated with aortic stiffness in untreated essential hypertension.

Metabolic syndrome is a powerful predictor of cardiovascular disease in hypertension, and large-artery stiffness is increasingly recognized as a cardiovascular risk factor. We hypothesized that the adverse prognostic significance of the metabolic syndrome in hypertension might be explained in part by its association with aortic stiffness. A total of 169 newly diagnosed, never treated, nondiabetic patients with essential hypertension (men 55%, 48+/-11 years) were classified by the presence (n=45) or absence (n=124) of the metabolic syndrome. All patients underwent aortic and upper limb pulse wave velocity determination by means of an applanation tonometry-based method. Aortic pulse wave velocity had a direct correlation with office and 24-hour systolic pressure (r=0.42 and 0.31, respectively), as well as with waist circumference (r=0.35, all P<0.001), but not with body mass index (r=0.10, P=not significant). Aortic pulse wave velocity was higher in the subgroup with the metabolic syndrome (10.0+/-2.7 versus 8.8+/-2.1 m/s; P=0.003), whereas upper limb velocity did not differ in the 2 groups (8.6+/-1.4 versus 8.7+/-1.5 m/s; P=not significant). In a multiple regression, aortic pulse wave velocity was independently associated with age, systolic blood pressure, and the metabolic syndrome. Only diastolic BP independently predicted upper limb pulse wave velocity. We conclude that in untreated hypertension, the metabolic syndrome is independently associated with a higher aortic, but not upper limb, pulse wave velocity. Central, but not general, adiposity is an important determinant of aortic stiffness in hypertension.

Abdomen↗

Precocious intima-media thickening in patients with primary Sjögren's syndrome.

OBJECTIVE: Systemic lupus erythematosus and rheumatoid arthritis represent independent risk factors for atherosclerosis (ATS), although this may be confounded by continuous pharmacologic treatment. Primary Sjögren's syndrome (SS) shares several features of these diseases and may therefore represent an interesting model for verifying the presence of accelerated ATS in the absence of pharmacologic interference. The present study therefore used this model to describe the presence of accelerated ATS in a group of young women. METHODS: Thirty-seven untreated white women with primary SS were evaluated clinically and serologically. Carotid and femoral artery intima-media thickness (IMT) was evaluated in the patients and in 35 age-matched healthy women who served as controls. RESULTS: The patients had a higher IMT than did the controls at both the carotid (mean +/- SD 0.82 +/- 0.24 mm versus 0.63 +/- 0.20 mm; P < or = 0.001) and the femoral (0.81 +/- 0.26 mm versus 0.67 +/- 0.23 mm; P < or = 0.019) levels, and had a higher prevalence of carotid intima-media thickening (49% versus 11% of controls; P < or = 0.001). The patient subset with high carotid IMT showed an increased prevalence of leukopenia and circulating anti-SSA antibodies; interestingly, the number of leukocytes was inversely correlated with the level of arterial IMT in patients with SS. Multivariate analysis demonstrated that anti-SSA antibodies were independent predictors of carotid artery thickening, while leukopenia was a predictor of both carotid and femoral artery thickening. CONCLUSION: Subclinical ATS was evident in about one-half of the patients with SS. Its association with some features typical of connective tissue diseases, such as the presence of anti-SSA and leukopenia, suggests that the immune dysregulation characterizing this autoimmune disorder may play a key role in inducing early ATS.

Adult↗

Plasma viscosity in isolated systolic hypertension: the role of pulse pressure.

Atherosclerosis is increasingly recognized as an inflammatory vascular disease, and high blood pressure (BP) has been suggested to exert a proinflammatory action. Whether plasma viscosity (PV), a major determinant of blood flow in microcirculation and a marker of systemic inflammation and cardiovascular risk, is increased in elderly subjects with isolated systolic hypertension is not known. In addition, the correlation of BP and its pulsatile component (ie, pulse pressure [PP]), with PV levels independent of the confounding effect of other cardiovascular risk factors has not been investigated. To this aim, we measured PV in 108 elderly men with never treated, uncomplicated isolated systolic hypertension, and in 60 healthy matched normotensive control subjects. The PV values were higher in hypertensive subjects than in controls (1.39+/-0.11 v 1.34+/-0.09 cP, P<.01). The PV showed a significant direct relation with both systolic BP (r=0.32) and PP (r=0.37, both P<.01), but not with diastolic BP (r=-0.03, P=.68). The PV was also directly associated with serum low-density lipoprotein cholesterol and triglycerides. In a multivariate analysis, PP was a significant predictor of PV levels when a consistent number of cardiovascular risk factors were simultaneously controlled for. In conclusion, PV is elevated in elderly subjects with isolated systolic hypertension. Systolic BP and PP appear to be major determinants of PV levels in these patients, independent of the potential proinflammatory action of traditional cardiovascular risk factors.

Aged↗

Acute inflammatory state during influenza infection and endothelial function.

Chronic inflammatory stimulus seems to contribute to atherosclerotic process. Several studies have established a relationship between infective agents as Chlamydia pneumoniae, herpes virus and cytomegalovirus and atherosclerotic lesions. Aim of this study was to investigate the effects of influenza infective state on endothelial function of healthy young subjects, expressed as brachial flow-mediated vasodilation (FMV) and soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). In 10 male subjects (mean age 35+/-14 years) exhibiting influenza symptoms for 3 days, we determined total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, sVCAM-1, sICAM-1 and brachial FMV. All subjects had an antibody pattern characteristic of influenza A or B virus infection. After 3 months brachial FMV was significantly increased (8.6+/-2.3% versus 11.5+/-3.2%; p<0.001), while HDL (46+/-10 mg/dL versus 49+/-9 mg/dL; p<0.05), sICAM-1 and sVCAM-1 were reduced (respectively: 488+/-105 ng/mL versus 340+/-127 ng/mL; p<0.001, 1710+/-80 ng/mL versus 1216+/-63 ng/mL; p<0.001). Univariate analysis showed a positive correlation between changes in CRP and sICAM-1 levels (r=0.95, p<0.001), a negative one between changes in sICAM-1 and brachial FMV (r=-0.65, p<0.05) and between CRP and brachial FMV (r=-0.64, p<0.05). This small study suggested that inflammatory state determined by viral agents may transitorily alter endothelial function in healthy subjects.

Acute Disease↗

Paraoxonase-1 activity modulates endothelial function in patients with peripheral arterial disease.

Human serum paraoxonase-1 (PON1) is thought to play a role in the favorable vascular effects of high-density lipoproteins, mainly through a reduction in low-density lipoprotein oxidation. Endothelial dysfunction, characterized by an impaired capacity of the arteries to dilate in response to a number of stimuli, represents the earliest stage of atherosclerosis. We performed the present study in 37 patients with peripheral arterial disease, with the aim of investigating the influence of PON1 Q192R polymorphism and activity on peripheral endothelial function, evaluated as brachial-artery flow-mediated vasodilation (FMV). Patients with the R allele (QR or RR genotype, n=19) had significantly higher PON1 activity [408 U/mL (309-456) versus 180 U/mL (141-243), p<0.001] and greater brachial FMV (5.7+/-3.9% versus 3.0+/-2.8%, p<0.001) than those with Q allele (QQ genotype, n=18). In the whole population, PON1 activity showed a direct relation to brachial FMV (r=0.46, p=0.004). In a multivariate linear regression analysis, the only independent predictors of brachial FMV were PON1 activity (beta=0.40, p=0.008), brachial-artery diameter (beta=-0.39, p=0.01) and male sex (beta=-0.27, p=0.04). These finding support the importance of PON1 activity as a modulating factor of the endothelial function.

Aged↗

Early atherosclerosis in rheumatoid arthritis: effects of smoking on thickness of the carotid artery intima media.

This study was designed to compare intima media thickness (IMT) of the carotid arteries among rheumatoid arthritis (RA) patients and controls and to determine whether disease-associated characteristics, smoking, and other classic risk factors for atherosclerosis are associated with IMT values. IMT was measured in the carotid arteries of 101 RA patients and 75 control subjects. The IMT was evaluated in the common carotid (CC), carotid bifurcation (BI), and internal carotid (IC). Eight IMT values were calculated including four mean and four maximal values of CC, BI, IC, and carotid artery (C). The following data were obtained for every patient: age, sex, body mass index (BMI), presence of erosions, extra-articular manifestations, rheumatoid factor, medications, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, daily number of cigarettes, number of smoking years, family history of cardiovascular diseases (CVD), and erythrocyte sedimentation rate (ESR) levels. RA patients had significantly higher mean-BI IMT than controls (1.02 mm vs. 0.89 mm; P < 0.01), higher incidence of increased mean-BI IMT and max-BI IMT, but lower incidence of increased max-IC IMT than controls. Factors significantly associated with IMT in the controls were age, BMI, and hypertension, whereas factors significantly associated with IMT in RA patients were age and smoking status. Mean carotid IMT was associated with all characteristics related to smoking in RA patients. Current smokers had higher mean carotid IMT and internal carotid artery IMT than former smokers. RA is associated with higher carotid artery bifurcation IMT. The profile of factors associated with IMT values is different between RA patients and controls. Smoking is an important factor augmenting early atherosclerosis in RA patients.

Adult↗

Prevalence of antiphospholipid and antioxidized low-density lipoprotein antibodies in rheumatoid arthritis.

Antiphospholipid antibodies characterize the antiphospholipid syndrome (APS), but they can also be found in various autoimmune, infectious, and malignant conditions. This study's objectives were to detect the prevalence of antiphospholipid and antioxidized low-density lipoprotein (anti-oxLDL) antibodies among patients with rheumatoid arthritis (RA) who did not have clinical manifestations of APS. Using a standard enzyme-linked immunosorbent assay (ELISA), we evaluated the levels of immunoglobulin G (IgG) and IgM anticardiolipin, IgG, and IgM anti-beta-2-glycoprotein-I (anti-beta(2)GPI), and anti-oxLDL autoantibodies in 82 patients with RA. The cutoff levels for detecting these autoantibodies were 15 IgG phospholipid units (GPL), 15 IgM phospholipid units (MPL), and 25 ELISA units (EU)/mL, respectively. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 10 with low levels of IgG anticardiolipin and 7 with medium to high levels of anticardiolipin autoantibodies. IgM anticardiolipin was found in only 1 (1%) patient, and both IgG and IgM anti-beta(2)GPI were found in 3 (4%) patients with RA. Elevated levels of anti-oxLDL antibodies were found in 8 (10%) patients, 4 of whom also had elevated levels of IgG anticardiolipin. We conclude that IgG anticardiolipin autoantibodies can be found in about one-fifth of RA patients who do not have clinical manifestations of APS. Whether the presence of anticardiolipin signifies increased risk for thrombosis and atherosclerosis in these patients should be studied further.

Antibodies, Anticardiolipin↗

Artichoke juice improves endothelial function in hyperlipemia.

Artichoke extracts have been shown to produce various pharmacological effects, such as the inhibition of cholesterol biosynthesis and of LDL oxidation. Endothelial dysfunction represents the first stage of atherosclerotic disease; it is usually evaluated in humans by a noninvasive ultrasound method as brachial flow-mediated vasodilation (FMV) and by the determination of several humoral markers such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. Aim of the study was to investigate the effects of dietary supplementation with artichoke juice on brachial FMV of hyperlipemics. We studied 18 moderately hyperlipemic patients (LDL cholesterol > 130 <200 mg/dl and/or triglycerides >150 <250 mg/dl) of both genders and 10 hyperlipemic patients, matched for age, sex and lipid parameters. All subjects were under isocaloric hypolipidic diet. A basal determination of serum lipids, soluble VCAM-1, ICAM-1, E-selectin and brachial FMV was performed. Thereafter patients were given 20 ml/die of frozen artichoke juice. The same parameters were repeated after 6 weeks. After artichoke treatment there was an increase of triglycerides (156 +/- 54 vs 165 +/- 76 mg/dL, p <0.05) and a reduction of total cholesterol (261 +/- 37 vs 244 +/- 38 mg/dL, p <0.05) and LDL cholesterol (174 +/- 31 vs 160 +/- 34 mg/dL, p <0.05). Controls showed a significant decrease in total and LDL cholesterol (respectively: 267 +/- 22 vs 249 +/- 20 mg/dL and 180 +/- 24 vs 164 +/- 23 mg/dL, both p <0.001). After artichoke there was a decrease in VCAM-1(1633 +/- 1293 vs 1139 +/- 883 ng/mL, p <0.05) and ICAM-1(477 +/- 123 vs 397 +/- 102 ng/mL, p <0.05), brachial FMV increased (3.3 +/- 2.7 vs 4.5 +/- 2.4%, p <0.01), while controls did not exhibit significant changes in VCAM-1, ICAM-1, E-selectin and brachial FMV. Univariate analysis showed that, in artichoke patients, changes of VCAM-1 and ICAM-1 were significantly related to changes in brachial FMV (respectively: r=-0.66 and r=-0.62; both p <0.05). In conclusion, artichoke dietary supplementation seems to positively modulate endothelial function in hypercholesterolemia.

Adult↗

Relevance of homocysteine on brachial flow-mediated vasodilatation and carotid and femoral intima-media thickness in patients with hypercholesterolemia.

The relevance of homocysteine to brachial flow-mediated vasodilatation and carotid and femoral intima-media thickness was investigated in 192 patients with hypercholesterolemia. Low-density lipoprotein cholesterol and homocysteine levels predicted brachial flow-mediated vasodilatation, internal carotid mean intima-media thickness, and intima-media thickening at all femoral sites. Homocysteine levels seem to be an additional factor in the initial atherosclerotic damage of patients with hypercholesterolemia.

Brachial Artery↗

CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients.

BACKGROUND: Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28null T cells and early atherosclerotic changes in RA has never been investigated. METHODS AND RESULTS: The number of circulating CD4+CD28null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-alpha led to a partial reappearance of the CD28 molecule on the CD4+ cell surface. CONCLUSIONS: Circulating CD4+CD28(null) lymphocytes are increased in RA. Patients with persistent CD4+CD28null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-alpha blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.

Aged↗

Prognostic value of the metabolic syndrome in essential hypertension.

OBJECTIVES: We sought to determine the prognostic significance of the metabolic syndrome in hypertension. BACKGROUND: Increased cardiovascular risk in hypertensive patients might be partially attributable to metabolic disturbances. METHODS: We prospectively followed for up to 10.5 years (mean 4.1 years) a total of 1742 hypertensive patients without cardiovascular disease (55% men; blood pressure [BP] 154/95 mm Hg; age 50 +/- 12 years). A modified National Cholesterol Education Program definition for metabolic syndrome was used, with body mass index in place of waist circumference. RESULTS: During follow-up, 162 patients developed cardiovascular events (2.28 events/100 patient-years). Event rates in the groups with one to five characteristics of the metabolic syndrome were 1.54, 1.96, 2.97, 3.35, and 5.27 per 100 patient-years, respectively (p < 0.001). A total of 593 patients (34%) had the metabolic syndrome. Patients with the syndrome had an almost double cardiovascular event rate than those without (3.23 vs. 1.76 per 100 patient-years, p < 0.001). After adjustment for age, gender, total cholesterol, creatinine, smoking, left ventricular hypertrophy, and 24-h systolic BP, the risk of developing cardiovascular events was still higher in patients with the metabolic syndrome (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.25 to 2.38). The syndrome was an independent predictor of both cardiac and cerebrovascular events (HRs 1.48 and 2.11, respectively). The adverse prognostic value of the metabolic syndrome was attenuated but still significant among the 1637 patients without diabetes (HR 1.43, 95% CI 1.02 to 2.08). CONCLUSIONS: In hypertensive subjects, the metabolic syndrome amplifies cardiovascular risk associated with high BP, independent of the effect of several traditional cardiovascular risk factors.

Adult↗

Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women.

Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.

Absorptiometry, Photon↗

Prognostic significance of isolated, non-specific left ventricular repolarization abnormalities in hypertension.

OBJECTIVE: Clinicians are often confronted with the incidental finding of isolated minor, non-specific repolarization changes on the electrocardiogram (ECG) in hypertensive patients. The aim of this study was to investigate the prognostic significance of such changes. DESIGN: Prospective, observational study. METHODS: A total of 1970 hypertensive patients without prevalent cardiovascular disease were followed for up to 9.1 years (mean 4.7 years). Patients with ECG abnormalities including ischaemia, previous infarction, bundle branch block, atrial fibrillation and ventricular pre-excitation were excluded. Patients were divided into three groups: normal left ventricular (LV) repolarization (n = 1355); minor repolarization changes (n = 504); and typical LV strain (n = 111). RESULTS: During follow-up, 78 patients developed new-onset ischaemic heart disease. The event rates were 0.50, 1.28 and 3.08 per 100 patient-years in the groups with normal repolarization, minor changes, and typical LV strain, respectively (P < 0.001). After adjustment for the effect of age, sex, diabetes, serum cholesterol, smoking, LV hypertrophy and 24-h pulse pressure, the risk for developing coronary events was higher in patients with minor repolarization changes (hazard ratio 2.07, 95% confidence interval 1.23-3.47; P < 0.01) or LV strain (hazard ratio 4.00, 95% confidence interval 2.09-7.65; P < 0.001) than in patients with normal repolarization (reference category). Population-attributable risks were 21 and 14%, respectively. Minor ST-T changes also retained an adverse prognostic value among patients without LV hypertrophy (hazard ratio 1.90, 95% confidence interval 1.08-3.33; P = 0.026). CONCLUSION: We have identified minor, non-specific LV repolarization changes as a novel, independent risk factor for ischaemic heart disease in patients with uncomplicated hypertension.

Adult↗