Ambulatory Resistant Hypertension and Risk of Heart Failure in the Elderly.

(1) Background: The aim of the study was to assess the risk of heart failure (HF) in elderly treated hypertensive patients with white coat uncontrolled hypertension (WUCH), ambulatory nonresistant hypertension (ANRH) and ambulatory resistant hypertension (ARH), when compared to those with controlled hypertension (CH). (2) We studied 745 treated hypertensive subjects older than 65 years. CH was defined as clinic blood pressure (BP) < 140/90 mmHg and 24-h BP < 130/80 mmHg; WUCH was defined as clinic BP ≥ 140/90 mmHg and 24-h BP < 130/80 mmHg; ANRH was defined as 24-h BP ≥ 130/80 mmHg in patients receiving ≤2 antihypertensive drugs; ARH was defined as 24-h BP ≥ 130/80 mmHg in patients receiving ≥3 antihypertensive drugs. (3) Results: 153 patients had CH, 153 had WUCH, 307 had ANRH and 132 (18%) had ARH. During the follow-up (8.4 ± 4.8 years), 82 HF events occurred. After adjustment for various covariates, when compared to CH, the hazard ratio (95% confidence interval) for HF was 1.30 (0.51-3.32), 2.14 (1.03-4.43) and 3.52 (1.56-7.96) in WUCH, ANRH and ARH, respectively. (4) Conclusions: among elderly treated hypertensive patients, those with ARH are at a considerably higher risk of developing HF when compared to CH.

Prognostic Impact of 24-Hour Pulse Pressure Components in Treated Hypertensive Patients Older Than 65 Years.

(1) Background: The aim of this study was to assess the prognostic impact of 24-hour pulse pressure (PP), elastic PP (elPP) and stiffening PP (stPP) in elderly treated hypertensive patients; (2) Methods: In this retrospective study, we evaluated 745 treated hypertensive subjects older than 65 years who underwent ambulatory blood pressure monitoring to assess 24-hour PP and 24-hour elPP and stPP, as calculated by a mathematical model. The association of these PP components with a combined endpoint of cardiovascular events was investigated; (3) Results: The 24-hour PP, elPP and stPP were 59 ± 12.5, 47.5 ± 9.5 and 11.5 ± 6.5 mmHg, respectively. During the follow-up (mean 8.4 years), 284 events occurred, including coronary events, stroke, heart failure hospitalization and peripheral revascularization. In the univariate Cox regression analysis, 24-hour PP, elPP and stPP were associated with the combined outcome. After the adjustment for covariates, per one standard deviation increase, 24-hour PP had a borderline association with risk (hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.00-1.34), 24-hour elPP remained associated with cardiovascular events (HR 1.20, 95% CI 1.05-1.36) and 24-hour stPP lost its significance. (4) Conclusions: 24-hour elPP is a predictor of cardiovascular events in elderly treated hypertensive patients.

Prediction of Masked Uncontrolled Hypertension Detected by Ambulatory Blood Pressure Monitoring.

The aim of this study was to provide prediction models for masked uncontrolled hypertension (MUCH) detected by ambulatory blood pressure (BP) monitoring in an Italian population. We studied 738 treated hypertensive patients with normal clinic BPs classified as having controlled hypertension (CH) or MUCH if their daytime BP was < or ≥135/85 mmHg regardless of nighttime BP, respectively, or CH or MUCH if their 24-h BP was < or ≥130/80 mmHg regardless of daytime or nighttime BP, respectively. We detected 215 (29%) and 275 (37%) patients with MUCH using daytime and 24-h BP thresholds, respectively. Multivariate logistic regression analysis showed that males, those with a smoking habit, left ventricular hypertrophy (LVH), and a clinic systolic BP between 130−139 mmHg and/or clinic diastolic BP between 85−89 mmHg were associated with MUCH. The area under the receiver operating characteristic curve showed good accuracy at 0.78 (95% CI 0.75−0.81, p < 0.0001) and 0.77 (95% CI 0.73−0.80, p < 0.0001) for MUCH defined by daytime and 24 h BP, respectively. Internal validation suggested a good predictive performance of the models. Males, those with a smoking habit, LVH, and high-normal clinic BP are indicators of MUCH and models including these factors provide good diagnostic accuracy in identifying this ambulatory BP phenotype.

Prognostic value of non-resistant and resistant masked uncontrolled hypertension detected by ambulatory blood pressure monitoring.

Masked uncontrolled hypertension (MUCH) is at higher cardiovascular risk than controlled hypertension (CH). In previous studies, patients with MUCH were considered as a unique group though those receiving ≤2 drugs could be defined as having nonresistant MUCH (NRMUCH) and those receiving ≥3 drugs as having resistant MUCH (RMUCH). The aim of this study was to assess the prognostic value of NRMUCH and RMUCH detected by ambulatory blood pressure (BP) monitoring. Cardiovascular risk was evaluated in 738 treated hypertensive patients with normal clinic BP. Patients were classified as having CH or MUCH if daytime BP < or ≥ 135/85 mmHg, respectively, regardless of nighttime BP, or CH or MUCH if 24-h BP < or ≥ 130/80 mmHg, respectively, regardless of daytime or nighttime BP. By daytime or 24-h BP, the authors detected 523 (71%), 178 (24%), and 37 (5%) or 463 (63%), 231 (31%), and 44 (6%) patients with CH, NRMUCH, and RMUCH, respectively. During the follow-up (median 10 years), 148 events occurred. After adjustment for covariates, compared to CH, the hazard ratio (HR), 95% confidence interval (CI), for cardiovascular events was 1.81, 1.27-2.57, and 2.99, 1.73-5.16, in NRMUCH and RMUCH defined by daytime BP, respectively, and 1.58, 1.12-2.23, and 2.21, 1.27-3.82, in NRMUCH and RMUCH defined by 24-h BP, respectively. If RMUCH was compared with NRMUCH, the risk tended to be higher in RMUCH but did not attain statistical significance (P = .08 and P = .23 by daytime and 24-h BP thresholds, respectively). In conclusion, both NRMUCH and RMUCH are at increased cardiovascular risk than CH.

Association of clinic and ambulatory blood pressure with new-onset atrial fibrillation: A meta-analysis of observational studies.

The aim of this study was to perform a meta-analysis of studies evaluating the association of clinic and daytime, nighttime, and 24-h blood pressure with the occurrence of new-onset atrial fibrillation. We conducted a literature search through PubMed, Web of science, and Cochrane Library for articles evaluating the occurrence of new-onset atrial fibrillation in relation to the above-mentioned blood pressure parameters and reporting adjusted hazard ratio and 95% confidence interval. We identified five studies. The pooled population consisted of 7224 patients who experienced 444 cases of atrial fibrillation. The overall adjusted hazard ratio (95% confidence interval) was 1.05 (0.98-1.13), 1.19 (1.11-1.27), 1.18 (1.11-1.26), and 1.23 (1.14-1.32), per 10-mmHg increment in clinic, daytime, nighttime, and 24-h systolic blood pressure, respectively. The degree of heterogeneity of the hazard ratio estimates across the studies (Q and I-squared statistics) were minimal. The results of this meta-analysis strongly suggest that ambulatory systolic blood pressure prospectively predicts incident atrial fibrillation better than does clinic systolic blood pressure and that daytime, nighttime, and 24-h systolic blood pressure are similarly associated with future atrial fibrillation.

Prognostic Value of Masked Uncontrolled Hypertension Defined by Different Ambulatory Blood Pressure Criteria.

BACKGROUND: Masked uncontrolled hypertension (MUCH), that is, nonhypertensive clinic but high out-of-office blood pressure (BP) in treated patients is at increased cardiovascular risk than controlled hypertension (CH), that is, nonhypertensive clinic and out-of-office BP. Using ambulatory BP, MUCH can be defined as daytime and/or nighttime and/or 24-hour BP above thresholds. It is unclear whether different definitions of MUCH have similar prognostic information. This study assessed the prognostic value of MUCH defined by different ambulatory BP criteria. METHODS: Cardiovascular events were evaluated in 738 treated hypertensive patients with nonhypertensive clinic BP. Among them, participants were classified as having CH or daytime MUCH (BP ≥135/85 mm Hg) regardless of nighttime BP (group 1), nighttime MUCH (BP ≥120/70 mm Hg) regardless of daytime BP (group 2), 24-hour MUCH (BP ≥130/80 mm Hg) regardless of daytime or nighttime BP (group 3), daytime MUCH only (group 4), nighttime MUCH only (group 5), and daytime + nighttime MUCH (group 6). RESULTS: We detected 215 (29%), 357 (48.5%), 275 (37%), 42 (5.5%),184 (25%) and 173 (23.5%) patients with MUCH from group 1 to 6, respectively. During the follow-up (10 ± 5 years), 148 events occurred in patients with CH and MUCH. After adjustment for covariates, compared with patients with CH, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 2.01 (1.45-2.79), 1.53 (1.09-2.15), 1.69 (1.22-2.34), 1.52 (0.80-2.91), 1.15 (0.74-1.80), and 2.29 (1.53-3.42) from group 1 to 6, respectively. CONCLUSIONS: The prognostic impact of MUCH defined according to various ambulatory BP definitions may be different.

Prognostic value of morning surge of blood pressure in middle-aged treated hypertensive patients.

We investigated the prognostic value of morning surge (MS) of blood pressure (BP) in middle-aged treated hypertensive patients. The occurrence of a composite end point (coronary events, stroke, and heart failure requiring hospitalization) was evaluated in 1073 middle-aged treated hypertensive patients (mean age 49 years). Patients with preawakening MS of BP above the 90th percentile (27/20.5 mm Hg for systolic/diastolic BP) were defined as having high MS of BP. During the follow-up (mean 10.9 years), 131 cardiovascular events occurred. After adjustment for various covariates, including known risk markers and ambulatory BP parameters, patients with high MS of systolic BP (hazard ratio 1.81, 95% confidence interval 1.10-2.96) and those with high MS of diastolic BP (hazard ratio 1.98, 95% confidence interval 1.19-3.28) were at higher cardiovascular risk than those with normal MS. In middle-aged treated hypertensive patients, high MS of systolic and diastolic BP is independently associated with increased cardiovascular risk.

Prognostic value of average real variability of systolic blood pressure in elderly treated hypertensive patients.

OBJECTIVE: The independent prognostic significance of ambulatory blood pressure variability in the elderly is incompletely clear. We investigated the prognostic value of average real variability of 24-hour blood pressure in elderly treated hypertensive patients. METHODS: The occurrence of a combined end-point including stroke, coronary events, heart failure requiring hospitalization and peripheral revascularization was evaluated in 757 elderly treated hypertensive patients. According to tertiles of average real variability of 24-hour systolic blood pressure patients were classified as having low (≤8.66 mmHg; n = 252), medium (8.67-10.05 mmHg; n = 252) or high (>10.05 mmHg; n = 253) average real variability. RESULTS: During the follow-up (6.9 ± 3.4 years, range 0.4-12.9 years), 195 events occurred. The event rate of the population was 3.74 per 100 patient-years. After adjustment for age, sex, previous events, diabetes, estimated glomerular filtration rate, left ventricular hypertrophy, left atrial enlargement, asymptomatic left ventricular systolic dysfunction at baseline, 24-hour systolic blood pressure, non-dipping and dipping with high morning surge of blood pressure, patients with high average real variability were at higher cardiovascular risk than those with low average real variability (hazard ratio 1.64, 95% confidence interval 1.12-2.40). CONCLUSIONS: In elderly treated hypertensive patients, high average real variability of 24-hour systolic blood pressure is associated with higher cardiovascular risk independently of other risk markers, average 24-hour systolic blood pressure and circadian blood pressure changes.

Myocardial glutathione metabolic status in fat-fed rabbits.

Short-term fat feeding could exert adverse cardiac effects by altering myocardial glutathione-related antioxidant defenses. We have here assessed total glutathione (TG), the activities of glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS), γ-glutamyl transpeptidase (γ-GT) and glutathione peroxidase (GSH-Px), fluorescent damage products of lipid peroxidation (FDPL), thiobarbituric acid-reactive substances (TBARS), H2O2, and ATP in the aerobically perfused hearts of control rabbits and of rabbits fed a fat-enriched diet for 18 days. Such biochemical parameters, myocardial hemodynamics and infarct size were assessed in the perfused hearts of other control and fat-fed rabbits subjected to 60 min global ischemia plus 30 min reperfusion. Compared to controls, a reduced activity of GSSG-Red and γ-GT associated with decreased TG content was detected in the aerobically perfused hearts of fat-fed rabbits, which also showed insignificant γ-GCS activation, GSH-Px depressed activity, FDPL, TBARS and H2O2 burden, and unaltered ATP content. Ischemia-reperfusion decreased the myocardial levels of TG, ATP, and γ-GCS activity and augmented those of FDPL, TBARS, and H2O2 especially in the fat-fed rabbits, without significant changes in myocardial GSSG-Red, γ-GT, and GSH-Px activities. Ischemia-reperfusion induced greater hemodynamic dysfunction and infarct size in the hearts of fat-fed rabbits than in those of controls. Thus, short-term fat feeding and hyperlipidemia alter glutathione metabolic status of the rabbit myocardium, inducing a GSSG-Red- and γ-GT-related decrement of myocardial glutathione content, which, together with GSH-Px dysfunction, may favor tissue oxidative stress and render the myocardium more susceptible to ischemia-reperfusion injury.

Prediction of carotid plaques in hypertensive patients by risk factors, left ventricular hypertrophy, and epicardial adipose tissue thickness.

Hypertension and other risk factors (RFs) predispose to carotid plaques (CPs). An association between left ventricular hypertrophy (LVH) or epicardial adipose tissue (EAT) and CPs has also been reported. The aim of the study was to evaluate whether the assessment of LVH and EAT thickness, beyond RFs, would be of additive value in predicting CPs in hypertensive subjects. We studied 548 hypertensive patients aged ≥ 50 years without carotid bruit. LVH and CPs were evaluated and defined according to standard criteria. EAT was measured by echocardiography above the free wall of the right ventricle at end diastole. The presence of LVH and EAT thickness above the median value (3.9 mm) together significantly increased prevalence of CPs in subjects with 0-1 risk factor, but not in those with ≥ 2 RFs who showed high prevalence of CPs independently of LVH and/or EAT. Receiver operating characteristic curve analysis showed that the addition of LVH and higher EAT thickness together significantly improved prediction of CPs in patients with 0-1 risk factor. Indeed, the area under the curve improved from 0.63 (0.56-0.69) to 0.73 (0.67-0.79), which was significantly higher (p < 0.05). In patients with ≥ 2 RFs, the addition of LVH and EAT did not significantly improve prediction of CPs. This study shows that the presence of LVH and higher EAT thickness together improves prediction of CPs in hypertensive patients with 0-1 risk factor and that those with ≥ 2 RFs show high prevalence of CPs independently of LVH and/or EAT.

Bicarbonate-dependent, carbonate radical anion-driven tocopherol-mediated human LDL peroxidation: an in vitro and in vivo study.

We have here investigated possible occurrence of bicarbonate-dependent, carbonate radical anion (CO(3)(•-))-driven tocopherol-mediated human LDL peroxidation (TMP) in vitro and in vivo. CO(3)(•-), generated in vitro by the SOD1/H(2)O(2)/bicarbonate system, readily promoted TMP, which was dependent on α-tocopherol and bicarbonate concentrations, and was inhibited by the CO(3)(•-) scavenger ethanol; moreover, TMP induced in vitro by the SOD1/H(2)O(2)/bicarbonate system occurred in the presence of α-tocopherol that typically underwent slow oxidative consumption. In the in vivo clinical setting, we showed that, compared to controls, hypertensive patients with diuretic-induced metabolic alkalosis and heightened blood bicarbonate concentration had lipid hydroperoxide burden and decreased α-tocopherol content in the LDL fraction, with direct significant correlation between the LDL levels of α-tocopherol and those of lipid hydroperoxides; remarkably, after resolution of metabolic alkalosis, together with normalization of blood bicarbonate concentration, the LDL content of lipid hydroperoxides was decreased and that of α-tocopherol augmented significantly. These findings suggest bicarbonate-dependent, CO(3)(•-)-driven LDL TMP in vivo. In conclusion, the present study highlights the occurrence of bicarbonate-dependent, CO(3)(•-)-driven human LDL TMP, the role of which in pathological conditions such as atherosclerosis warrants, however, further investigation.

Cardiac events in hypertensive patients with renal artery stenosis treated with renal angioplasty or drug therapy: meta-analysis of randomized trials.

BACKGROUND: Cardiac outcome in patients with atherosclerotic renal artery stenosis (ARAS) undergoing percutaneous transluminal renal angioplasty (PTRA) or medical therapy is not yet completely clear. The aim of this study was to perform a meta-analysis of randomized controlled trials to compare the effect of PTRA and medical therapy on nonfatal myocardial infarction in patients with ARAS. METHODS: We searched for articles reporting cardiovascular outcome, including nonfatal myocardial infarction, in patients with renal artery stenosis randomized to PTRA with/without stenting or medical therapy. RESULTS: Five studies were identified. The pooled population consisted of 1,159 subjects who experienced 56 nonfatal myocardial infarctions. When compared with medical therapy, the overall relative risk (RR) was 0.85 (95% confidence interval (CI) 0.51-1.42), P = 0.55, for PTRA. There was no significant difference between PTRA and medical therapy according to procedural characteristics (with/without stent placement), mean serum creatinine at follow-up (higher or lower than 2.0 mg/dl), and maximum follow-up length (> or <2 years). CONCLUSIONS: In patients with ARAS and hypertension, there is a lack of evidence supporting the superiority of PTRA over medical therapy in prevention of nonfatal myocardial infarction. Awaiting for results of ongoing trials, our data and previous data suggest that PTRA and drug therapy have a similar impact on cardiovascular risk reduction in patients with renal artery stenosis and hypertension.

Endogenous secretory RAGE in obese women: association with platelet activation and oxidative stress.

CONTEXT: The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis. OBJECTIVE: We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk. PATIENTS: Eighty otherwise healthy obese women and 20 nonobese women were studied. RESULTS: esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13-0.26) vs. 0.38 (0.20-0.48) ng/ml, P = 0.003; and 4.4 (2.8-6.4) vs. 10.0 (6.9-12.5) µg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [544 (402-698) vs. 149 (98-219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2). CONCLUSION: In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.

Platelet function in health and disease: from molecular mechanisms, redox considerations to novel therapeutic opportunities.

Increased oxidative stress appears to be of fundamental importance in the pathogenesis and development of several disease processes. Indeed, it is well known that reactive oxygen species (ROS) exert critical regulatory functions within the vascular wall, and it is, therefore, plausible that platelets represent a relevant target for their action. Platelet activation cascade (including receptor-mediated tethering to the endothelium, rolling, firm adhesion, aggregation, and thrombus formation) is tightly regulated. In addition to already well-defined platelet regulatory factors, ROS may participate in the regulation of platelet activation. It is already established that enhanced ROS release from the vascular wall can indirectly affect platelet activity by scavenging nitric oxide (NO), thereby decreasing the antiplatelet properties of endothelium. On the other hand, recent data suggest that platelets themselves generate ROS, which may evoke pro-thrombotic responses, triggering many biological processes participating in atherosclerosis initiation, progression, and complication. That oxidative stress may alter platelet function is conceivable when considering that antioxidants play a role in the prevention of cardiovascular disease, although the precise mechanism accounting for changes attributable to antioxidants in atherosclerosis remains unknown. It is possible that the effects of antioxidants may be a consequence of their enhancing or promoting the antiplatelet effects of NO derived from both endothelial cells and platelets. This review focuses on current knowledge regarding ROS-dependent regulation of platelet function in health and disease, and summarizes in vitro and in vivo evidence for their physiological and potential therapeutic relevance.

Cardiovascular risk and dietary sugar intake: is the link so sweet?

Soft drinks and sugar-sweetened beverages have been targeted as one of the primary culprits in the escalating rates of obesity and diabetes and reduction of added sugars is considered between the goals to achieve in order to promote cardiovascular health and to reduce deaths from cardiovascular causes. Many reliable mechanisms, such as dislypidemia, inflammation and enhanced oxidative stress, have been proposed to support a causal link between sugar sweetened beverages intake and cardiovascular risk, but the ultimate underlying pathways remain to be determined in adequately designed studies. Furthermore, while epidemiological evidence strongly supports an association between sugar sweetened beverages consumption and obesity, type 2 diabetes mellitus or cardiovascular risk, incongruous findings yielded by clinical trials, or formal meta-analyses make difficult to draw firm conclusions in this regard. Further and rigorous studies are needed to better understand the role of sugar sweetened beverages in the etiology of cardiovascular diseases and to better address the warnings and decisions of regulatory authorities on public health worldwide.

Diabetes mellitus and thrombosis.

Atherothrombosis is the leading cause of morbidity and mortality in patients with diabetes mellitus. Several mechanisms contribute to the diabetic prothrombotic state, including endothelial dysfunction, coagulative activation and platelet hyper-reactivity. In particular, diabetic platelets are characterised by dysregulation of several signaling pathways leading to enhanced adhesion, activation and aggregation. These alterations result from the interaction among hyperglycemia, insulin resistance, inflammation and oxidative stress. This review will provide an overview of the current status of knowledge on mechanisms of accelerated atherothrombosis in patients with diabetes mellitus.

Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost.

Platelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB2 and 8-iso-PGF(2α) excretion rate, as in vivo indexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB2 [499 (277-807) vs. 380 (189-560) pg/mg creatinine, p < 0.0001] and 8-iso-PGF(2α) [533 (316-842) vs. 334 (196-540) pg/mg creatinine, p < 0.0001] as well as plasma sCD40L [1540 (1005-3015) vs. 948 (845-2030) pg/ml, p < 0.0001]. Furthermore, a significant increase in plasma nitrate plus nitrite levels has been observed [26.8 (18.8-35.9) vs. 43.7 (33.0-75.5) µM, p < 0.0001]. A significant direct correlation was also found between urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 before and after iloprost treatment (Rho = 0.695, p < 0.0001). In conclusion, we report that a short-term course of iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.

Serum albumin and biomolecular oxidative damage of human atherosclerotic plaques.

OBJECTIVES: To investigate the association of serum albumin (SA) with oxidative damage of human atherosclerotic plaques and the severity of atherosclerosis. DESIGN AND METHODS: Correlation of the levels of SA with those of lipid and protein oxidation of endarterectomy-removed carotid atherosclerotic plaques; SA and plaque oxidative biomarkers comparison between 2 groups of patients with different severity of atherosclerotic carotid stenosis, i.e. <90% (group I) or ≥90% (group II). RESULTS: SA was strongly inversely correlated with plaque oxidative damage; SA was lower and plaque oxidative damage higher in group II than group I. CONCLUSIONS: Lowered SA is associated with oxidative damage of atherosclerotic plaques and the severity of atherosclerosis.

Soluble forms of RAGE in internal medicine.

The receptor for advanced glycation end-products (RAGE) and its ligands are intimately involved in the pathobiology of a wide range of diseases that share common features, such as enhanced oxidative stress, immune/inflammatory responses, and altered cell functions. Soluble forms of RAGE (sRAGE), including the splice variant endogenous secretory (es)RAGE, have been found circulating in plasma and tissues. Experimental data suggest that these isoforms may neutralize the ligand-mediated damage by acting as a decoy. Moreover, evidence is mounting to support a role for both sRAGE and esRAGE as biomarkers or endogenous protection factors against RAGE-mediated pathogenesis. In this review, we will focus on clinical and therapeutical implications arising from studies investigating the significance of soluble RAGE isoforms in several clinical settings, including cardiovascular disease, diabetes mellitus, hypercholesterolemia, chronic renal failure, immune/inflammatory diseases, pulmonary diseases, neurodegeneration, and cancer.