Incidence Of Vascular Disease Research Articles

Hypertriglyceridaemic waist phenotype criteria and prevalent metabolic triad in women

To assess the metabolic profile and the prevalence of the metabolic triad (i.e. hyperinsulinaemia, hyperapobetalipoproteinaemia, and decreased low-density lipoprotein particle size) in women characterized by the hypertriglyceridaemic waist (HTGW) phenotype and to identify cut-off values for triglycerides and waist circumference, effectively discriminating women with the metabolic triad. Two hundred and twenty-eight female subjects without any history of vascular disease or diabetes mellitus attending an Outpatient Lipid Clinic setting at the University Hospital of Ioannina, Greece were studied. Currently available HTGW criteria for women were unable to detect any significant differences in the metabolic profile either in the pre- or post-menopausal women, and proved similar in terms of sensitivity and specificity in identifying women with the metabolic triad. A cut-off value of 1.26 mmol/L for triglycerides and 84.5 cm for waist circumference were determined by Receiver-operating Curve evaluation. Women with both triglycerides and waist circumference above these thresholds had four-fold higher odds of presenting with the metabolic triad compared with women with non-HTGW phenotype. A HTGW phenotype definition of 1.26 mmol/L for triglycerides and 84.5 cm for waist circumference may effectively identify Mediterranean women with the atherogenic metabolic triad. Whether these criteria are also associated with a higher incidence of vascular disease and/or new-onset diabetes in women remains to be investigated.

Soluble CD40 Ligand Predicts Ischemic Stroke and Myocardial Infarction in Patients With Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is associated with a high incidence of vascular disease that may be related to a prothrombotic and inflammatory state. Soluble CD40 ligand (sCD40L), which stems essentially from platelet activation, possesses inflammatory and prothrombotic properties. The aim of the study was to assess whether sCD40L is a predictor of stroke or myocardial infarction (MI) in patients with nonvalvular AF. Plasma levels of sCD40L were measured in 231 patients (177 [77%] had permanent or persistent AF, and 54 [23%] had paroxysmal AF). Patients were followed for a mean period of 27.8+/-8.8 months, and cardiovascular events such as fatal and nonfatal stroke and MI were recorded. AF population was divided in 2 groups according to sCD40L level above or below the median (4.76 ng/mL). The 2 patients' groups had similar distribution of cardiovascular risk factors, age, gender, medications, or serum C-reactive protein levels. During the follow-up period, vascular events occurred in 6 (2 nonfatal MI and 4 nonfatal ischemic strokes) of 116 patients with low levels of sCD40L (5.1%) and in 29 (11 fatal and 3 nonfatal MI; 3 fatal and 12 nonfatal ischemic strokes) of 115 patients with high levels (25.2%) (log-rank test: P<0.001). Using the COX proportional Hazards model, patients with sCD40L above the median were 4.63 times more likely to experience a vascular event (95% C.I.: 1.92 to 11.20). This study shows that enhanced soluble CD40L level is a predictor of vascular events in patients with nonvalvular AF, thus suggesting that enhanced platelet activation may play a role in its clinical progression.

Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease

High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L). Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. clinicaltrials.gov Identifier: NCT00032435.

The role of dialysis in contrast-induced nephropathy: doubts and certainties

Over past years, there has been a progressive increase in percutaneous endovascular procedures in patients with chronic renal disease, owing to the high incidence of vascular disease, particularly coronary artery disease, in this population. The use of contrast media may further worsen renal function in such patients, in some cases even accelerating the progression towards end-stage renal failure, and may increase patient morbidity and mortality. In this review, we discuss the role of dialysis in preventing contrast-induced nephropathy as well as present indications to its use in patients already on dialysis treatment undergoing diagnostic or therapeutic procedures with contrast medium injection.

Antibodies toward High‐Density Lipoprotein Components Inhibit Paraoxonase Activity in Patients with Systemic Lupus Erythematosus

Patients with systemic lupus erythematosus (SLE) have an increased incidence of vascular disease, and oxidative stress is recognized as an important feature in this condition, despite the underlying mechanisms not being fully understood. In these patients, an interaction between lipoproteins and the immune system has been suggested, but most studies have only looked at antibodies against oxidized low-density lipoproteins. This study was undertaken to determine the presence of antibodies directed against high-density lipoproteins (HDL) and to identify a possible association between these antibodies and paraoxonase (PON), an antioxidant enzyme present in HDL. Plasma from 55 patients with SLE was collected and IgG aHDL and antiapolipoprotein A-I (aApo A-I) antibodies were assessed by enzyme-linked immunosorbent assay. Standardization of the method was performed in a control population of 150 healthy subjects. Plasma levels above 5 standard deviations of the mean of the control population were considered positive. PON activity was assessed by quantification of p-nitrophenol formation (micromol/mL/min). Patients with SLE had higher titers of aHDL (P < 0.0001) and aApo A-I (P < 0.0001) antibodies, and lower PON activity (P < 0.0001) than healthy controls. There was also a direct correlation between the titers of aHDL and aApo A-I antibodies (r = 0.61; P < 0.0001). PON activity was inversely correlated with aApo A-I (P = 0.0129) antibody levels. Anti-HDL and aApo A-I antibodies from patients with high titers were isolated and subsequently incubated with human HDL. These antibodies reduced PON activity up to a maximum of 70.2% and 78.4%, respectively. This study showed the presence of aHDL and aApo A-I antibodies in patients with SLE. These antibodies were associated with reduced PON activity in plasma, and the in vitro inhibition assay confirmed a direct inhibition of the enzyme activity.

Short-Term Hyperhomocysteinemia-Induced Oxidative Stress Activates Retinal Glial Cells and Increases Vascular Endothelial Growth Factor Expression in Rat Retina

Hyperhomocysteinemia is associated with an increase in the incidence of vascular diseases, including retinal vascular diseases. We examined the effects of high plasma levels of homocysteine on retinal glial cells and vascular endothelial growth factor (VEGF) expression. Male Sprague-Dawley rats were fed either a 3.0 g/kg homocystine diet or a control diet for 2 week. The homocystine-diet group had higher plasma levels of homocysteine and thiobarbituric acid reactive substances (TBARSs) and lower plasma levels of folate, retinol, alpha-tocopherol, and retinal expression of CuZn superoxide dismutase (SOD) than the controls. The rats fed the homocystine-diet showed an increase in vimentin, glial fibrillary acidic protein (GFAP), and VEGF immunoreactivity in the retina as compared to the controls. The increase in vimentin immunoreactivity in the hyperhomocysteinemic rats was correlated with changes in GFAP immunoreactivity in astrocytes within the ganglion cell layer. We found for the first time that short-term hyperhomocysteinemia-induced oxidative stress activates retinal glial cells and increases VEGF expression in the retina.

High-density lipoprotein and transport of cholesterol and triglyceride in blood

High-density lipoproteins (HDL) contain approximately 25% of the cholesterol and <5% of the triglyceride in the plasma of human blood. However, the dynamic exchange of lipids and lipid-binding proteins is not revealed by simply considering the mass of material at any point in time. HDL are the most complex of lipoprotein species with multiple protein constituents, which facilitate cholesterol secretion from cells, cholesterol esterification in plasma, and transfer of cholesterol to other lipoproteins and to the liver for excretion. They also play a major role in triglyceride transport by providing for activation of lipoprotein lipase, exchange of triglyceride among the lipoproteins, and removal of triglyceride rich remnants of chylomicrons and very-low–density lipoproteins after lipase action. In addition, antioxidative enzymes and phospholipid transfer proteins are important components of HDL. Many of the proteins of HDL are exchangeable with other lipoproteins, including chylomicrons and very-low–density lipoproteins. The constantly changing content of lipids and apolipoproteins in HDL particles generate a series of structures that can be analyzed by using separation techniques that depend on size or charge of the particles. Interaction of these various structures can be very different with cell surfaces depending on the size or apolipoprotein content. A series of different transport proteins preferentially exchange lipids with specific structures among the HDL but interact poorly or not at all with others. The role of these differing forms of HDL and their interactions with cells and other lipoprotein species in plasma is the subject of intense study stimulated by the potential for reducing atherogenesis. The strength of this is only partially indicated by the correlation of higher total levels of the HDL particles with reduced incidence of vascular disease in various clinical trials and epidemiological studies.

New possibilities of genotypic in the prediction of the likelihood of autoimmune diseases

The purpose of the study was to estimate the incidence of thyroid dysfunction and cardiovascular diseases in perimenopausal females. The cross-sectional study covered 554 females (mean age 52.6±6.1 years). The levels of thyroid-stimulating hormone (TSH), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL), the incidence of arterial hypertension (AH), coronary heart disease, chronic heart failure, myocardial infarction, cerebral circulatory disorders, and the severity of menopausal syndrome (MS) were determined. The study detected euthyroldism in 381 (68.8%) patients, hypothyroidism in 168 (30.3%), out of them 35 (20.8%) patients having primary hypothyroidism, and hyperthyroidism in 5 (0.9%) females. Out of the 133 patients receiving L-thyroxine therapy, hypothyroidism was compensated. In 78(58.7%) cases, the dose of L-thyroxine was inadequate. The level of LDL was significantly higher in hypothyroidism; the median of TC was higher than the normal levels in both groups. There were no differences in the incidence of vascular disease between the groups. In both groups, AH was encountered In more than 60% of cases. The females with hypothyroidism had a more severe course of MS. With the adequate dose of L-thyroxine, the level of HDL was significantly higher and that of triglycerides and VLDL was lower than in hypothyroidism. It is expedient to include the measurement of TSH levels into the algorithm of examination of patients with severe MS.

Incidence of thyroid and cardiovascular diseases in menopausal females

The purpose of the study was to estimate the incidence of thyroid dysfunction and cardiovascular diseases in perimenopausal females. The cross-sectional study covered 554 females (mean age 52.6±6.1 years). The levels of thyroid-stimulating hormone (TSH), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL), the incidence of arterial hypertension (AH), coronary heart disease, chronic heart failure, myocardial infarction, cerebral circulatory disorders, and the severity of menopausal syndrome (MS) were determined. The study detected euthyroldism in 381 (68.8%) patients, hypothyroidism in 168 (30.3%), out of them 35 (20.8%) patients having primary hypothyroidism, and hyperthyroidism in 5 (0.9%) females. Out of the 133 patients receiving L-thyroxine therapy, hypothyroidism was compensated. In 78(58.7%) cases, the dose of L-thyroxine was inadequate. The level of LDL was significantly higher in hypothyroidism; the median of TC was higher than the normal levels in both groups. There were no differences in the incidence of vascular disease between the groups. In both groups, AH was encountered In more than 60% of cases. The females with hypothyroidism had a more severe course of MS. With the adequate dose of L-thyroxine, the level of HDL was significantly higher and that of triglycerides and VLDL was lower than in hypothyroidism. It is expedient to include the measurement of TSH levels into the algorithm of examination of patients with severe MS.

Dimethylthetin treatment causes diffuse alveolar lung damage: A pilot study in a sheep model of Continuous Ambulatory Peritoneal Dialysis (CAPD)

Total plasma homocysteine (Hcy) concentration correlates with risk of vascular disease. Over 80% of chronic renal failure patients have elevated plasma Hcy and a 10–20 times higher incidence of vascular disease. Glycine betaine lowers plasma Hcy through methylation catalysed by betaine-homocysteine methyltransferase (BHMT). Dimethylthetin (DMT), a synthetic glycine betaine analogue, is a more effective BHMT substrate. DMT is therefore a potential therapeutic agent for reducing plasma Hcy in humans and may be particularly useful in renal failure patients receiving dialysis because of chronic betaine depletion as a result of treatment. We aimed to determine whether the addition of DMT to dialysis fluid lowered plasma Hcy concentrations in a Continuous Ambulatory Peritoneal Dialysis sheep model using animals that were either in acute renal failure ( n = 3 ) or had normal renal function ( n = 1 ). Sub-acute exposure to DMT was toxic to all four animals, which died with total lung consolidation and collapse and Diffuse Alveolar Damage within 48 h of beginning treatment. Adverse side effects were observed after 4–8 doses. DMT was not detected in pre-dialysis plasma samples and the final concentration at death was 0.5–7.8 mmol/L, depending on the number of doses each animal was exposed to. Abnormalities were not observed in animals supplied standard dialysis fluid, or fluid with added glycine betaine. Toxicity associated with DMT treatment raises concerns for its use in further studies. However, sub-acute administration of DMT to sheep may provide a useful model of acute alveolar damage.

Smoking causes erectile dysfunction through vascular disease

Objectives To investigate whether smoking either directly or through vascular disease causes erectile dysfunction (ED) and to determine whether ED is an early marker of vascular disease in smokers. Methods The target population consisted of all men 50, 60, or 70 years old who resided in the study areas in Finland in 1994. Questionnaires were mailed to 3143 men in 1994, to 2837 men in 1999, and to 2510 men in 2004. A total of 1368 men (55% of those alive) responded to the three surveys. Results Men who smoked in 1994 and developed a vascular disease during 1994 to 1999 had a three times (adjusted incidence density ratio [IDR] 3.1, 95% confidence interval [CI] 1.3 to 7.5) greater risk of ED during 1999 to 2004 compared with those who had never smoked who did not develop vascular disease. In contrast, smokers without episodes of vascular disease were not at an increased risk of ED (adjusted IDR 1.0, 95% CI 0.5 to 1.8). Among men who were exsmokers and had ED in 1994, the incidence of vascular disease was greater than among those who had never smoked who were free of ED at entry (IDR 1.5, 95% CI 1.0 to 2.2). No greater risk of vascular disease owing to ED was found in smokers (IDR 1.1, 95% CI 0.6 to 2.0) or those who had never smoked (IDR 1.1, 95% CI 0.6 to 1.9) at entry. Conclusions The results of this study have shown that smoking may cause ED because it can cause vascular disease, and ED may be a marker of silent vascular disease in exsmokers.

Lipoproetin pattern in patients with chronic renal failure and those who had renal transplantation

Background: Vascular disease is common in patients with chronic renal failure as well as in patients with renal transplantation. It is a common cause of death in these patients. One possible factor for this increased incidence of vascular disease is hyperlipidaemia that frequently occurs in these patients. Purpose: To determine the lipoprotein pattern in patients with chronic renal failure and patients who had renal transplantation in our community. Methods: 78 patients, age ranging between 10-75 years (mean value of 42.7) were studied. They were 21 pre-dialysis patients, 42 dialyzed patients (20 peritoneal dialysis and 22 Haemodialysis), and 15 patients following renal transplantation. Fasting blood Cholesterol, triglyceride, high and low density lipoprotein (HDL and LDL) were determined. Results: 2 patients of the pre-dialysis group had high cholesterol levels, while 6 patients had high triglyceride levels and 7 patients had high serum HDL levels. Only 9 patients had ischaemic changes on E.C.Gs. 3(7.3%) patients on dialysis group had high cholesterol levels, 11.9% had high triglyceride levels. 24 patients of the dialysis group had ischaemic changes in E.C.G. 7 transplant patients had high serum triglyceride levels and only two have elevated LDL. Sudan Journal of Medical Sciences Vol. 1(1) 2006: 37-40

L’étude SU.VI.MAX, un essai contrôlé randomisé, en double aveugle, testant l’effet de la supplémentation en vitamins et minéraux antioxydants sur la santé

The SU.VI.MAX study is a double blind, randomized, placebo-controlled trial testing, for 7,5 years, the effect of a combination of antioxidant vitamins and minerals, at doses considered to be nutritional (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium and 20 mg zinc) in reducing cancer and ischemic vascular disease incidence in a general population (12.741 middle-aged). After 7.5 years, low-dose antioxidant supplementation had no effect on vascular disease incidence. This dose lowered, however, total cancer incidence in men, but not in women. With regard to contradictory results of observational and interventional studies published for the last decades, we can consider that the effect of antioxidants on cancer may depend on the doses (nutritional versus pharmacological), baseline antioxidant status (different between gender and/or nutritional status) and health status of subjects (healthy versus cancer high-risk subjects). Antioxidant supplementation may have a beneficial effect on cancer incidence only in healthy subjects who are not exposed to cancer risk, and with a particularly low baseline status. Finally, antioxidants as well as free radicals appear to be ambiguous nutrients with a wide range of benefits and toxicity. High doses of antioxidant supplements may be deleterious in high-risk subjects without any clinical symptoms in whom the initial phase of cancer development has already started.

Differential inhibition by hyperglycaemia of shear stress‐ but not acetylcholine‐mediated dilatation in the iliac artery of the anaesthetized pig

Clinical hyperglycaemia affects vascular endothelial function, but the effect on shear stress-induced arterial dilatation has not yet been established. We hypothesized that hyperglycaemia would inhibit this response via impaired glycocalyx mechanotransduction. Experiments were carried out in the anaesthetized pig in which pressure, blood flow and diameter of the left iliac artery were measured at two sites: proximal (d1) and distal (d2). Infusion of glucose, sufficient to raise blood glucose to 16-30 mm along the whole length of the artery, attenuated the shear stress-dependent dilatation in both sections of the artery with preservation of the responses to acetylcholine. The distal site was then isolated using snares and the lumen exposed to blood containing 25-35 mm glucose for 20 min. In the control situation, after exposure of both sections to normoglycaemia (5.7 mm glucose), both sections of artery showed increases in diameter in response to shear stress and acetylcholine. Hyperglycaemia attenuated the shear stress-dependent dilatation in the distal section only (P < 0.25), but not the response to acetylcholine. It is concluded from these results that the hyperglycaemia-impaired dilatation is consistent with loss of mechanotransducing properties of the endothelial glycocalyx by hyperglycaemia. These findings offer a possible explanation for the increased incidence of vascular disease in diabetic patients.

Effets biologiques des anti-oxydants : les données de l’étude SU.VI.MAX

The SU.VI.MAX study is a double blind, randomised, placebo-controlled trial testing, for 8 years, the effect of a combination of antioxidant vitamins and minerals, at doses considered to be nutritional (120 mg vitamin C, 30 mg vitamin E, 6mg beta-carotene, 100 lg selenium and 20 mg zinc) in reducing cancer and ischaemic vascular disease incidence in a general population (12,741 middleaged). After 7.5 years, low-dose antioxidant supplementation had no effect on vascular disease incidence. This dose lowered, however, total cancer incidence in men, but not in women. With regard to contradictory results of observational and interventional studies published for the last decades, we can consider that the effect of antioxidant on cancer may depend on the doses (nutritional versus pharmacological), baseline antioxidant status (different between gender and/or nutritional status) and health status of subjects (healthy versus cancer high-risk subjects). Antioxidant supplementation may have a beneficial effect on cancer incidence only in healthy subjects who are not exposed to cancer risk, and with a particularly low baseline status. Finally, antioxidants as well as free radicals appear to be ambiguous nutrients with a wide range of benefits and toxicity. High doses of antioxidant supplements may be deleterious in high-risk subjects without any clinical symptoms in whom the initial phase of cancer development has already started.

Differential responsiveness of early- and late-passage endothelial cells to shear stress

Background The incidence of vascular disease increases with age. Because atherosclerosis and neointimal hyperplasia colocalize in areas of disturbed shear stress, the effects of orbital shear stress (SS) on endothelial cell proliferation, protein kinase B (Akt) activation, and functional activity were analyzed using a senescence model. Methods Early- (p3 to 7) and late- (p28 to 32) passage bovine aortic endothelial cells were exposed to orbital SS (210 rpm) or static conditions (0 to 5 days). Cell proliferation was directly counted and confirmed with proliferating cell nuclear antigen reactivity. Phosphorylated and total Akt were assessed with Western blotting. Endothelial cell–induced smooth muscle cell migration was assessed with a Boyden chamber. Results Late-passage endothelial cells demonstrated no increase in orbital SS stimulated proliferation compared with early-passage cells ( P = .42). Late-passage endothelial cells demonstrated decreased Akt phosphorylation in response to SS compared with early passage cells (n = 6, P = .01). Late-passage cells induced 26% less smooth muscle cell migration than early-passage cells (n = 3, P = .03). Conclusions Late-passage endothelial cells demonstrate decreased proliferation, Akt phosphorylation, and secretion of smooth muscle cell chemoattractants in response to orbital SS compared with early passage cells. These results suggest that late-passage endothelial cells respond to SS differently than early-passage cells and confirm the utility of the in vitro senescence model.

Analysis of the apolipoprotein(a) size polymorphism in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by an increased incidence of vascular disease which is only partially explained by traditional risk factors. Previous reports suggested that the level of lipoprotein(a) [Lp(a)], a particle linked to atherothrombotic disorders, is increased in patients with SLE. However, whether there are any differences in the distribution of apolipoprotein(a) [apo(a)] phenotypes between SLE patients and healthy controls remain to be determined. To address this issue, Lp(a) levels and apo(a) isoform size were analyzed in a total of 54 patients with SLE and in 108 age- and gender-matched healthy controls. SLE patients showed Lp(a) levels [median (interquartile range): 25.3 (6.5-51.0) vs. 9.5 (4.6-25.9) mg/dl, P=0.0109)] and a percentage of subjects with at least one small-sized apo(a) isoform (< or =25 K-IV repeats) significantly higher than controls (44.44% vs. 25.92%, P=0.0277). Multiple regression analysis adjusting for age, gender, disease duration, kidney involvement, the presence of active disease, as well as the carriage of at least one small apo(a) isoform revealed that only small apo(a) phenotypes were significant predictors of Lp(a) levels in SLE patients (P=0.0001). We conclude that genetic factors related to apo(a) size are a major determinant of elevated Lp(a) levels in patients with SLE. As small apo(a) phenotypes have been related to adverse vascular effects, it is feasible that small apo(a) isoforms may be a useful biological marker in the assessment of vascular risk in patients with SLE.

Regional Differences in Viscosity, Elasticity, and Wall Buffering Function in Systemic Arteries: Pulse Wave Analysis of the Arterial Pressure-Diameter Relationship

Regional variations in the incidence of vascular diseases have been related to regional differences in arterial viscoelasticity. The aim of this study was to characterize the differences in the elastic and viscous modulus and in wall buffering function between central and peripheral systemic arteries, through a time-series analysis of the pressure-diameter relationship. Pressure and diameter were measured in seven arterial segments (carotid, brachiocephalic trunk, ascending aorta, proximal, middle and distal descending thoracic aorta, and femoral artery) from six sheep. Each segment was mounted on an in vitro mock circulatory system and perfused with Tyrode solution, with a pulse frequency of 1.8 Hz and systemic pressure levels. We used the Kelvin-Voigt model to calculate the pressure-diameter elastic (Epd, mmHg/mm) and viscous (Vpd, mmHg.s/mm) modulus, and to quantify the local wall buffering function (Vpd/Epd). We also calculated the incremental Young's and pressure-strain elastic modulus and pulse wave velocity for each segment. The elastic and viscous modulus increased from proximal to distal segments. The wall buffering function did not differ significantly between arteries. The lower rigidity of the central arteries compared to the distal ones may indicate that the systolic arterial compliance function is concentrated in the central arterial segments. On the other hand, the greater viscosity in the distal segments may indicate that viscous energy loss is concentrated in these segments. Arterial elasticity and viscosity can be interpreted as properties that are dependent on the region of the vessel, whereas wall buffering function can be considered region-independent.

Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis

Methotrexate (MTX) is a folate analogue used in the treatment of moderate to severe psoriasis and rheumatoid arthritis (RA). It oppositely affects inflammation and hyperhomocysteinemia-two independent risk factors for vascular disease. To date, there are no published reports evaluating the impact of these potentially paradoxical action of MTX. The purpose of this study was to evaluate the effect of MTX therapy on the incidence of vascular disease in patients with psoriasis and RA. We conducted a retrospective cohort study in which we analyzed computerized records of 7,615 outpatients diagnosed with psoriasis and 6,707 with RA at the Veterans Integrated Service Network 8. Patients prescribed MTX therapy had a significantly reduced risk of vascular disease compared to those who were not prescribed MTX (psoriasis: RR = 0.73, 95% CI = 0.55-0.98; RA: 0.83, 0.71-0.96). This reduction was most evident for patients prescribed a low cumulative dose of MTX (psoriasis: RR = 0.50, 95% CI = 0.31-0.79; RA = 0.65, 0.52-0.80). Concomitant use of folic acid (FA) with MTX also reduced the incidence of vascular disease in patients prescribed MTX (psoriasis: RR = 0.56, 95% CI = 0.39-0.80; RA: 0.77, 0.38-1.56). MTX therapy reduced the incidence of vascular disease in veterans with psoriasis or RA. Low to moderate cumulative dose appears more beneficial than the higher dose. We hypothesize that this effect is caused by its anti-inflammatory properties. In addition, a combination of MTX and FA led to a further reduction in the incidence of vascular disease.

Hormone Replacement Therapy and Peripheral Vascular Disease in Women

Women have been shown to have a lower incidence of vascular disease when compared to men. However, the incidence of vascular disease increases as women progress through menopause and reaches an incidence similar to that of men later in life. Women with peripheral vascular disease often have a delay in diagnosis, a higher incidence of asymptomatic disease, and poorer outcome after interventions. The differences in outcome have been attributed to a number of factors such as anatomic and hormonal differences. It is thought that estrogen deficiency is at least partially responsible for the increased risk of developing vascular disease after menopause, and thus hormone replacement therapy has been considered as a method to prevent progression of vascular disease. Conclusions drawn from a number of recent studies have resulted in a divergent view of hormone replacement therapy (HRT). This article explores the risk of peripheral vascular disease in women and the current state of research on hormone replacement therapy. The aims of this review are to present current perspectives on gender differences in the pathogenesis and outcomes of peripheral arterial disease (PAD). The effect of estrogen on atherogenesis, the role it plays in modulating the vascular endothelium, and the current evidence of the effects of HRT on vascular pathology is discussed. The most recent HRT clinical trials and present evidence for the benefits and risks of postmenopausal hormone replacement therapy are summarized. The effect of these issues on treatment practices is explained and suggestions are made for future directions of HRT and PAD research.