1,721,030 research outputs found
Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia
No full textObjectives: Community-acquired pneumonia (CAP) is associated with low-grade endotoxemia but its relationship with cardiovascular events (CVE) has not been investigated.Methods: We evaluated the incidence of CVE including myocardial infarction, stroke, and cardiovascular death in 523 adult patients hospitalized for CAP. Serum lipopolysaccharide (LPS) and zonulin, a marker of gut permeability, were analyzed in the cohort, that was followed-up during hospitalization and up to 43 months thereafter.Results: During the hospital-stay, 55 patients experienced CVE with a progressive increase from the lowest (0.6%) to highest LPS tertile (23.6%, p < 0.001). Logistic regression analyses showed that higher LPS tertile was independently associated with CVE; LPS significantly correlated with age, hs-CRP and zonulin. In a subgroup of 23 CAP patients, blood E. coli DNA was higher in patients compared to 24 controls and correlated with LPS. During the long-term follow-up, 102 new CVE were registered; the highest tertile of LPS levels was associated with incident CVE; Cox regression analysis showed that LPS tertiles, age, history of CHD, and diabetes independently predicted CVE.Conclusions: In CAP low-grade endotoxemia is associated to short- and long-term risk of CVE. Further study is necessary to assess if lowering LPS by non-absorbable antibiotics may result in improved outcomes. (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association
Gut dysbiosis-derived low-grade endotoxemia. a common soil for liver and cardiovascular disease
No full textGut dysbiosis is characterized by bacteria overgrowth that ultimately leads to increased intestinal barrier permeability and translocation of bacteria or bacterial products such as lipopolysaccharide (LPS) in the portal and, eventually, systemic circulation. Intestinal epithelial cells and hepatocytes possess enzymatic armamentarium to counteract the LPS toxic effect, however, impaired degradation results in LPS accumulation in the hepatocytes and endothelial wall. Experimental and clinical studies documented that in patients with liver disease, such as nonalcoholic fatty acid liver disease (NAFLD), low-grade endotoxemia caused by LPS is implicated in liver inflammation and thrombosis via interaction with its Toll-like receptor 4 (TLR4) expressed by hepatocytes and platelets. Furthermore, studies in patients with severe atherosclerosis documented that LPS localizes in atherosclerotic plaque in close association with activated macrophages expressing TLR4 suggesting LPS's role in vascular inflammation, atherosclerotic progression, and thrombosis. Finally, LPS may directly interact with myocardial cells to induce electric and functional changes leading to atrial fibrillation or heart failure. This review will focus on experimental and clinical evidence suggesting that low-grade endotoxemia, as a mechanism, potentially accounts for vascular damage occurring at the level of the hepatic and systemic circulation and myocardial cells
Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding
No full textAnti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B2 and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB2 value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB2 was -6.5% with warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban (p<0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB2 (B: -0.469, p<0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB2 in the NOACs group (Rs: 0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2 excretion compared to warfarin, suggesting that NOACs possess antiplatelet propert
Risk of venous thromboembolism and arterial events in patients with hypoalbuminemia: a comprehensive meta-analysis of more than 2 million patients
Full text linkBackground: Albumin has antiplatelet and anticoagulant functions. Hypoalbuminemia, as defined by serum values of <3.5 g/dL, is associated with arterial thrombosis; its impact on venous thromboembolism (VTE) is unclear. Objectives: The objective of this meta-analysis is to assess the VTE risk in patients with hypoalbuminemia. Methods: MEDLINE and EMBASE were searched up to January 2024 for observational studies and randomized trials reporting data of interest. Primary outcome was the risk of VTE, while secondary outcomes were myocardial infarction and stroke risk in patients with hypoalbuminemia versus those without hypoalbuminemia. The risk of bias was evaluated using Newcastle-Ottawa scale and Cochrane tool. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. Results: Forty-three studies for a total of 2 531 091 patients (39 738 medical and 2 491353 surgical) were included in primary analysis; 79.1% of the studies used 3.5 g/dL cut-off value for hypoalbuminemia definition. Follow-up duration was 30 days in 60.5% of studies. Patients with hypoalbuminemia had a higher risk of VTE (RR, 1.88; 95% CI, 1.66-2.13). RRs were similar in both medical (RR, 1.87; 95% CI, 1.53-2.27) and surgical patients (RR, 1.87; 95% CI, 1.61-2.16) and in patients with (RR, 1.86; 95% CI, 1.66-2.10) and without cancer (RR, 1.89; 95% CI, 1.47-2.44). Risk of myocardial infarction (RR, 1.88; 95% CI, 1.54-2.31) and stroke (RR, 1.77; 95% CI, 1.26-2.48) was higher in patients with hypoalbuminemia. Conclusion: Hypoalbuminemia is a risk factor for VTE in both medical and surgical patients irrespective of cancer coexistence. Serum albumin analysis may represent a simple and cheap tool to identify patients at VTE risk
Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation
Full text linkAging is strictly associated with an increased incidence of cardiovascular events (CVEs) in the general population. Mechanisms underlying the risk of CVEs are still unclear. Platelet activation contributes to the onset of cardiovascular complications. The incidence of atrial fibrillation (AF) increases with age, and the natural history of AF is often complicated by CVEs. We prospectively investigated the relationship between age, urinary thromboxane (Tx) B2, which reflects platelet activation, and CVEs in 833 AF patients. Median TxB2 level was 120 [66-200] ng/mg of urinary creatinine. At multivariable linear regression analysis, age (B: 0.097, p=0.005) and previous MI/CHD (B: 0.069, p=0.047) were associated with log-TxB2 levels. When we divided our population into age classes (i.e. < 60, 60-69, 70-79, ≥ 80 years), we found a significant difference in TxB2 levels across classes (p=0.005), with a significant elevation at 74.6 years. During a mean follow-up of 40.9 months, 128 CVEs occurred; the rate of CVEs significantly increased with age classes (Log-rank test, p < 0.001). TxB2 levels were higher in patients with, compared to those without, CVEs in patients aged 70-79 (p < 0.001) and ≥ 80 (p = 0.020) years. In conclusion, TxB2 levels enhance by increasing age, suggesting that platelet activation contributes to CVEs in elderly patients with AF
Mediterranean diet reduces Thromboxane A2 production in atrial fibrillation patients
No full textBACKGROUND & AIMS:
Platelet activation plays a major role in cardiovascular events (CVEs). Mediterranean diet (Med-Diet) reduces the incidence of stroke and myocardial infarction but it is still unclear if it affects platelet activation. Aim of the study was to evaluate the effect of Med-Diet on the urinary excretion of 11-dehydro-thromboxane (Tx) B2, a marker of in vivo platelet activation, in patients with atrial fibrillation (AF).
METHODS:
Prospective observational cohort study including 801 non-valvular AF patients on chronic treatment with warfarin/acenocumarol referring to I Medical Clinic - Atherothrombosis Center of Sapienza University of Rome, Italy, from February 2008 to December 2013. Adherence to Med-Diet was evaluated by a short nine-items dietary questionnaire. Urinary excretion of 11-dehydro-TxB2 was measured in all patients.
RESULTS:
Mean follow-up was 33.9 (±19.8) months, yielding 2223 patient/year of observation. Mean age of patients was 73.3 (±8.9) years, 43.7% were female. Median value of urinary TxB2 was 105.5 [60.0-190.0] ng/mg creatinine. We found a significant inverse correlation between total Med-Diet score and 11-dehydro-TxB2 values (Rs: -0.356, p < 0.001). In a multivariable stepwise linear regression analysis, history of stroke/TIA (β = 0.146, p = 0.003), olive oil (β = -0.130, p = 0.007), wine (β = -0.102, p = 0.036) and antiplatelet drugs (β = -0.098, p = 0.045) were independently associated to 11-dehydro-TxB2. We found no differences in the rate of ischemic or bleeding events across tertiles of Med-Diet score during follow-up.
CONCLUSIONS:
Med-Diet adherence is inversely associated to urinary excretion of 11-dehydro-TxB2, suggesting that Med-Diet may favorably affect platelet function in AF patients. Clinical Trial Registration ClinicalTrials.gov NCT01882114
Extra virgin olive oil blunt post-prandial oxidative stress via NOX2 down-regulation.
No full textObjective: Olive oil protects against cardiovascular disease but the underlying mechanism is still unclear.
We speculated that olive oil could inhibit oxidative stress, which is believed to be implicated in the
atherosclerotic process.
Methods and results: Post-prandial oxidative stress and endothelial dysfunction were investigated in
twenty-five healthy subjects who were randomly allocated in a cross-over design to a Mediterranean diet
added with or without extra virgin olive oil (EVOO, 10 g) (first study, n 1⁄4 25) or Mediterranean diet with
EVOO (10 g) or corn oil (10 g) (second study, n 1⁄4 25). Oxidative stress biomarkers including platelet
reactive oxidant species (ROS) and 8-iso-PGF2a-III, activity of NOX2, the catalytic sub-unit of NADPH
oxidase, as assessed in platelets and serum, serum vitamin E and endothelial dysfunction, were measured
before and 2 h after lunch.
In the first study a significant increase of platelet ROS, 8-iso-PGF2a-III, NOX2 activity, sE-selectin,
sVCAM1 and a decrease of serum vitamin E were detected in controls but not when EVOO was
included in the Mediterranean diet; oxidative stress and endothelial dysfunction increase were also
observed in the second study in subjects given corn oil. A significant correlation was found between
NOX2 activity and platelet oxidative stress. In vitro study demonstrated that EVOO but not corn oil
significantly decreased platelet and PMNs oxidative stress and NOX2 activity.
Conclusion: The study provides the first evidence that post-prandial oxidative stress may be triggered by
NOX2 up-regulation. EVOO but not corn oil, is able to counteract such phenomenon suggesting that
addition of EVOO to a Mediterranean diet protects against post-prandial oxidative stress
High cardiovascular risk in non-alcoholic fatty liver disease: a possible role for increased oxidative stress.
No full textShort-term in vivo modifications of platelet NADPH oxidase 2 (NOX2) and prostaglandin F2α in HIV-1 patients on abacavir-based therapies
No full textOBJECTIVES:
The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress.
METHODS:
We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F2α (8-iso-PGF2α ). Platelet activation was measured by soluble CD40L (sCD40L).
RESULTS:
At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups.
CONCLUSIONS:
ABC reduced platelet sNOX2-dp and 8-iso-PGF2α in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups
Association of proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with abnormally high ankle-brachial index in atrial fibrillation
No full textBackground: High ankle-brachial index (ABI) has been associated with increased risk of worse out-comes in the general population. Few data on atrial fibrillation (AF) exist. Experimental data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) contributes to vascular calcification but clinical data on this association are lacking. Aims: We wanted to investigate the relationship between circulating PCSK9 levels and an abnormally high ABI in patients suffering from AF. Methods: We analyzed data from 579 patients included in the prospective ATHERO-AF study. An ABI >= 1.4 was considered high. PCSK9 levels were measured coincidentally with ABI measurement. We used optimized cut-offs of PCSK9 for both ABI and mortality obtained from Receiver Operator Characteristic (ROC) curve analysis. All-cause mortality according to the ABI value was also analyzed. Results: One hundred and fifteen patients (19.9%) had an ABI >= 1.4. The mean (standard deviation [SD]) age was 72.1 (7.6) years, and 42.1% of patients were women. Patients with ABI >= 1.4 were older, more frequently male, and diabetic. Multivariable logistic regression analysis showed an association between ABI >= 1.4 and serum levels of PCSK9 >1150 pg/ml (odds ratio [OR], 1.649; 95% confidence interval [CI], 1.047-2.598; P = 0.031). During a median follow-up of 41 months, 113 deaths occurred. In multivariable Cox regression analysis, an ABI >= 1.4 (hazard ratio [HR], 1.626; 95% CI, 1.024-2.582; P = 0.039), CHA2DS2-VASc score (HR, 1.249; 95% CI, 1.088-1.434; P = 0.002), antiplatelet drug use (HR, 1.775; 95% CI, 1.153-2.733; P = 0.009), and PCSK9 >2060 pg/ml (HR, 2.200; 95% CI, 1.437-3.369; P <0.001) were associated with all-cause death. Conclusions: In AF patients, PCSK9 levels relate to an abnormally high ABI >= 1.4. Our data suggest PCSK9 role in contributing to vascular calcification in AF patients
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