The relation between hostility and concurrent levels of inflammation is sex,age, and measure dependent

Background and objective

Hostility may be associated with greater systemic inflammation. However, contradictory evidence exists. Certain individuals or dimensions of hostility may be more susceptible to these effects. Main and interactive effects of hostility with sex and/or age were evaluated on markers of inflammation, independently of traditional risk factors for coronary artery disease.

Methods

199 healthy men (81) and women (118), aged 20–64 years (M = 41 ± 11 years) were recruited. Hostility was assessed using the Cook–Medley Hostility Inventory (CMHo) and ecological momentary assessments (EMA) of quarrelsome behavior and angry affect in daily living. Blood samples were drawn to measure inflammatory activity (Il-6, TNF-α, hsCRP, Il-8, Il-10, Il-18, MCP-1) and lipid oxidation (Myeloperoxidase; MPO). Correlations and hierarchical regression analyses were performed controlling for pertinent behavioral, psychological, medical, and socio-demographic factors.

Results

Significant univariate associations emerged between CMHo and Il-6, TNF-α, MCP-1 (p < .05). Hierarchical regressions showed interactions of hostility with sex (Il-6, TNF-α; p < .05) and age (hsCRP, Il-6, TNF-α; p < .05). For example, in simple slope analyses, hostility was positively related to TNF-α in women (b = 0.009, p = 0.006) but not men. Greater hostility was also related to greater Il-6 levels among younger women (b = . 027, p = 0.000).

Conclusion

Hostility, particularly cynical hostility, may be detrimental to (younger) women. The TNF-α, Il-6, CRP triad appears vulnerable to psychological and behavioral factors, and may be one mechanism by which cynical hostility (CMHo) contributes to increased cardiovascular risk in women. Prospective research is needed to verify this.     

Sustained high plasma plasminogen activator inhibitor-1 levels are associated with severity and mortality in septic patients

Background

Higher plasma plasminogen activator inhibitor-1 (PAI-1) levels have been reported in septic patients. However, some questions remain unanswered, such as whether there is an association between plasma PAI-1 levels and sepsis severity and mortality, and inflammation state during the first week.

Methods

Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units of 260 patients with severe sepsis. Circulating levels of PAI-1 and tumour necrosis factor (TNF)-α were measured at day 1, 4 and 8. End-point was 30-day mortality.

Results

Nonsurviving septic patients (n = 89) presented higher PAI-1 levels than surviving (n = 171) at day 1 (58.4 (33.3-83.8) vs 36.5 (21.1-62.5) ng/mL; p < 0.001), 4 (34.0 (14.7-53.3) vs 16.2 (10.2-27.4) ng/mL; p < 0.001) and 8 (30.6 (16.2-47.8) vs 18.9 (10.4-29.5) ng/mL; p = 0.004). We found a positive correlation of PAI-1 levels with SOFA, lactic acid, aPTT, INR and TNF-α, and negative with platelet count at day 1, 4 and 8. Logistic regression analyses showed that PAI-1 levels at day 1 (p < 0.001), 4 (p < 0.001) and 8 (p = 0.001) were associated with 30-day mortality. On ROC curve analysis to predict 30- day survival, the area under the curve of PAI-1 levels at day 1, 4 and 8 were 0.65 (95% CI = 0.58-0.72; p < 0.001), 0.69 (95% CI = 0.60-0.78; p < 0.001) and 0.65 (95% CI = 0.54-0.75; p = 0.005) respectively.

Conclusions

The most interesting findings of our study, to our knowledge the largest series reporting PAI-1 levels during follow-up in septic patients, were that plasma PAI-1 levels during the first week were associated with inflammation, severity and mortality.     

Low molecular weight heparin-induced increase in chylomicron-remnants clearance,is associated with decreased plasma TNF-α level and increased hepatic lipase activity

Objective

The acute effect of heparin on lipoprotein clearance is well characterized. Yet, the effect of prolonged low-molecular-weight-heparin (LMWH) administration on post-prandial lipemia has remained so far unexplored. Recent reports suggest that LMWH could modify lipid and carbohydrate metabolism by diminishing TNFα-mediated inflammatory response. This, together with the known negative effect of TNF-α on insulin sensitivity, prompted us to hypothesize that LMWH would favorably affect post-prandial lipoprotein disposal.

Methods

Twenty four patients were given a vitamin A-fat loading meal at the end of 6-week enoxaparin treatment and after 3-month washout period. Post-prandial lipemia was assessed by measuring retinyl-palmitate (RP) during 8 hours following the meal. Insulin sensitivity index (ISI), plasma lipolytic activity and plasma TNF-α were measured.

Results

Enoxaparin did not impact fasting plasma lipids and lipoproteins levels. Enoxaparin increased RP clearance in the chylomicron remnant (CMR) fraction by 32% (P < 0.01). Additionally, enoxaparin decreased plasma TNF-α by 22% (P < 0.01), increased hepatic lipase (HL) activity by 81% (P < 0.01), along with a 2-fold increase in ISI (P < 0.01). The decrease in CMR correlated with the reduction in TNFα and the increase in ISI and HL activity (R = 0.48, -0.68, - 0.56, respectively, p < 0.05). Significant correlations were also found between the reduction in TNFα and both the increase in ISI and increase in HL activity (R = - 0.43, -0.54, respectively, P < 0.05).

Conclusions

The association of the effect on post-prandial metabolism, plasma TNFα level and HL activity during prolonged enoxaparin treatment may support the hypothesis that the beneficial outcome of enoxaparin may possibly be linked to anti-inflammatory and lipase-potentiating impact.     

Diabetes,depressive symptoms,and inflammation in older adults: Results from the Health,Aging, and Body Composition Study

Objective

Up-regulated levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) are common to both type 2 diabetes mellitus (T2DM) and elevated depressive symptoms, yet little attention has been given to the biological mechanisms associated with these co-morbidities. This study examined the association between inflammation and both T2DM and elevated depressive symptoms.

Methods

Baseline data were analyzed from 3009 adults, aged 70–79, participating in the Health, Aging, and Body Composition Study. Diabetes was assessed per self-report, medication use, fasting glucose and/or glucose tolerance tests. Elevated depressive symptoms were categorized using the Center for Epidemiologic Studies Depression scale (cut-score ≥ 20). Log-transformed IL-6, TNF-α, and CRP were analyzed using ANCOVA.

Results

Participants with T2DM and elevated depressive symptoms (T2DM + DEP n = 14) demonstrated significantly (p < .05) higher IL-6 compared to (T2DM Only n = 628), (DEP Only n = 49), and (No T2DM or DEP n = 2067) groups following covariate adjustment. Similarly, participants with T2DM + DEP (n = 14) had significantly (p < .05) higher CRP, after covariate adjustment, compared to DEP Only (n = 50) and No T2DM or DEP groups (n = 2153). No association was observed for TNF-α.

Conclusions

These findings provide evidence that inflammation is associated with T2DM and elevated depressive symptoms. Participants with T2DM + DEP demonstrated the highest IL-6 levels compared to all other groups. Greater CRP levels were also observed in T2DM, but not elevated depressive symptoms, which may suggest that differential associations between T2DM and depressive symptoms exist for various inflammatory markers. Further investigation into these associations could aid in understanding the biological pathways underlying both T2DM and depressive symptoms.     

Efficacy of postoperative anticoagulation therapy with enoxaparin for portal vein thrombosis after hepatic resection in patients with liver cancer

Backgrounds

Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery.

Study design

A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n = 228) and an enoxaparin (+) group (n = 53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared.

Results

In the enoxaparin (+) group, the patients’ age (65 vs. 69 years; p = 0.01) and BMI (22.9 vs. 24.4; p < 0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p = 0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p = 0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49).

Conclusions

Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers.     

Pathological gambling in eating disorders: Prevalence and clinical implications

Objective

Pathological gambling (PG) and eating disorders (ED) rarely co-occur. We explored the prevalence of lifetime PG in ED, compared severity of ED symptoms, personality traits, and psychopathological profiles across individuals with ED and PG (ED + PG) and without PG (ED-PG). Finally, we assessed the incremental predictive value of gender on the presentation of a comorbid PG.

Method

A total sample of 1681 consecutively admitted ED patients (1576 females and 105 males), participated in the current study (25 ED + PG and 1656 ED-PG). All participants were diagnosed according to DSM-IV criteria. Assessment measures included the Symptom Checklist and the Temperament and Character Inventory-Revised, as well as other clinical and psychopathological indices.

Results

The observed lifetime prevalence of PG was 1.49%. ED subtype was associated with lifetime PG (p = .003), with PG being more frequent in binge eating disorder (5.7%). ED + PG was more prevalent in males than in females (16% vs. 1.26%, respectively). Additionally, ED + PG patients exhibited more impulsive behaviours, lower impulse regulation and higher novelty seeking. Best predictors of ED + PG were novelty seeking (OR 1.030, p = .035), sex (OR 3.295, p = .048) and BMI (OR 1.081, p = .005).

Conclusions

Some personality traits (novelty seeking), being male and higher BMI are strongly related to the presence of lifetime PG in specific ED subtypes (namely binge eating disorder).     

oxLDL – the molecule linking hypercoagulability with the presence of cardiovascular disease in hemodialyzed uraemic patients

Introduction

Patients with end-stage renal disease (ESRD) exhibit features of a hypercoagulable state, which may contribute to cardiovascular complications. Data from “in vitro” studies suggest that cell-free plasma lipids and lipoproteins may be capable to support thrombin generation. The aim of this study has been to establish the role of plasma oxidized LDL (oxLDL) in the coagulation activation in hemodialyzed (HD) patients with and without cardiovascular disease (CVD).

Materials and Methods

We examined relationship between a marker of coagulation activation – prothrombin fragments 1 + 2 (F_1 + 2), and plasma oxLDL levels in 60 HD patients with and without CVD and in 20 healthy controls.

Results

F_1 + 2 levels were significantly higher in HD patients than in controls, and they were higher in HD patients with CVD compared to those without CVD (p < 0.001). Conversely, oxLDL levels were similar in HD patients with CVD and healthy controls, whereas this parameter was lower in HD patients without CVD when compared to controls and patients with CVD (both p < 0.01). Close positive and independent association was between F_1 + 2 and oxLDL levels in HD patients. Nitrates treatment and the presence of pyelonephritis were associated with reduced oxLDL as well as hypercoagulability in HD patients with cardiovascular complications.

Conclusion

This study demonstrates the independent association between oxLDL and the marker of coagulation activation - F_1 + 2 in HD patients. This new observation may offer a better understanding of the complex mechanism leading to hypercoagulability, which is markedly intensified in these patients, particularly in those with CVD.     

Genetic determinants of acenocoumarol and warfarin maintenance dose requirements in Slavic population: A potential role of CYP4F2 and GGCX polymorphisms

Introduction

VKORC1 and cytochrome CYP2C9 genetic variants contribute largely to inter-individual variations in vitamin K antagonists (VKAs) dose requirements. Cytochrome P450 4 F2 isoform (CYP4F2), gamma-glutamyl carboxylase (GGCX) and apolipoprotein E (APOE) polymorphisms have been suggested to be of minor significance.

Materials and Methods

We sought to assess the impact of those polymorphisms on dose requirements in Central-Eastern European cohort of 479 patients receiving acenocoumarol (n = 260) or warfarin (n = 219).

Results

There were no differences between the acenocoumarol and warfarin groups with regard to the gender, age, body mass index and international normalized ratio. The VKORC1 c.-1639A allele carriers required a lower dose of acenocoumarol and warfarin than the non-carriers (28.0 [21.0–35.0] vs. 42.0 [28.0–56.0] mg/week, p < 0.0001; 35.0 [28.0–52.0] vs. 52.0 [35.0–70.0] mg/week, p = 0.0001, respectively). Carriers of *2 and/or *3 variant alleles for CYP2C9 also required a lower dose of warfarin as compared with *1*1 carriers (35.0 [31.5–52.5] vs. 43.8 [35.0–60.2] mg/week, p = 0.02; 35.0 [23.5–35.0] vs. 43.8 [35.0-60.2] mg/week, p < 0.0001, respectively). Similarly, possession of G allele of GGCX c.2084 + 45 polymorphism was associated with lower warfarin dose (35.0 [26.3–39.2] vs. 45.5 [35.0–65.1] mg/week, p = 0.03). No effect of CYP2C9*2,-*3 and GGCX c.2084 + 45G > C polymorphisms on acenocoumarol dosage was observed. Interestingly, carriers of CYP4F2 c.1297A variant required a higher dose of acenocoumarol and warfarin than non-carriers (43.8 [35.0–60.2] vs. 35.0 [35.0–52.5] mg/week, p = 0.01; 35.0 [28.0–52.5] vs. 28.0 [28.0–42.0] mg/week, p = 0.05).

Conclusions

We have shown for the first time, that besides VKORC1 and CYP2C9 genetic variants, the CYP4F2 c.1297A and GGCX c.2084 + 45G have a moderate effect on VKAs dose requirements in Slavic population from Central-Eastern Europe.     

Familiarity and face emotion recognition in patients with schizophrenia

Objective

To assess the emotion recognition in familiar and unknown faces in a sample of schizophrenic patients and healthy controls.

Methods

Face emotion recognition of 18 outpatients diagnosed with schizophrenia (DSM-IVTR) and 18 healthy volunteers was assessed with two Emotion Recognition Tasks using familiar faces and unknown faces. Each subject was accompanied by 4 familiar people (parents, siblings or friends), which were photographed by expressing the 6 Ekman’s basic emotions. Face emotion recognition in familiar faces was assessed with this ad hoc instrument. In each case, the patient scored (from 1 to 10) the subjective familiarity and affective valence corresponding to each person.

Results

Patients with schizophrenia not only showed a deficit in the recognition of emotions on unknown faces (p = .01), but they also showed an even more pronounced deficit on familiar faces (p = .001). Controls had a similar success rate in the unknown faces task (mean: 18 +/− 2.2) and the familiar face task (mean: 17.4 +/− 3). However, patients had a significantly lower score in the familiar faces task (mean: 13.2 +/− 3.8) than in the unknown faces task (mean: 16 +/− 2.4; p < .05). In both tests, the highest number of errors was with emotions of anger and fear. Subjectively, the patient group showed a lower level of familiarity and emotional valence to their respective relatives (p < .01).

Conclusions

The sense of familiarity may be a factor involved in the face emotion recognition and it may be disturbed in schizophrenia.     

Inhibitory effects of bortezomib on platelet aggregation in patients with multiple myeloma

Introduction

Multiple myeloma (MM) therapy affects prothrombotic and anticoagulant processes. Patients receiving thalidomide, especially in combination with steroids, are at increased risk of venous thromboembolism (VTE), while the incidence of VTE on bortezomib is low. In vitro studies indicate that bortezomib causes a reduction in ADP-induced platelet aggregation.

Objectives

To analyse the influence of bortezomib on platelet aggregation induced by various agonists in patients with MM.

Patients and Methods

A total of 30 patients (median age 57.5 years) with relapsed/refractory MM receiving bortezomib-based regimens were analysed. Optical platelet aggregometry was performed with the agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The results from two groups: those treated with bortezomib and thalidomide (BT group, n = 11) and those without thalidomide (B group, n = 19) were analysed.

Results

During the second cycle, significantly decreased platelet aggregation was observed in the B group: 5 μM ADP (p = 0.0285, day 1 versus 8); 3.5 μM ADP (p = 0.0005, day 1 versus 8 and day 1 versus 11), collagen (p = 0.0014, day 4 versus 8, day 4 versus 11), 1.25 mg/ml ristocetin (p = 0.0017, day 1 versus 8 and day 1 versus 11). Agonist-induced platelet aggregation tended to be reduced over time during the 1st cycle in group B. In the thalidomide group, significant platelet aggregation inhibition by collagen only was found. Transient reduction in platelet count was observed in all patients, but more prominently in group B.

Conclusion

The inhibitory effects of prolonged exposure of bortezomib on platelet aggregation were demonstrated in relapsed/refractory MM patients, but antithrombotic activity of bortezomib should be clarified in further prospective studies.     

A genetic association study of D-dimer levels with 50 K SNPs from a candidate gene chip in four ethnic groups

Introduction

D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.

Materials and Methods

We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.

Results

Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p < 2.0 × 10^− 6. The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p = 0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p = 0.006). No additional SNPs were significantly associated with D-dimer.

Conclusions

Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.     

Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers

Objective

Serotonin modulates human behavior and emotion. Recent evidence implies that a higher level of serotonergic activity could be associated with a higher level of perceived social support. This study aimed to examine the correlation between serotonin transporter (SERT) availability and perceived social support scores in healthy volunteers.

Methods

111 healthy participants, 50 males and 61 females, were enrolled from the community and completed the Measurement of Support Function questionnaire. Single photon emission computed tomography (SPECT) with [¹²³I] ADAM was performed to examine SERT availability.

Results

Perceived social support was positively correlated with SERT availability (Spearman's ρ = 0.29, p < 0.01; χ² = 7.57, p < 0.01), particularly in males (Spearman's ρ = 0.37, p < 0 .01; χ² = 11.77, p < 0.01). Censored regressions indicated that these associations are not influenced by a ceiling effect and remained significant after controlling the effect of age.

Conclusions

This result confirmed the correlation between perceived social support and central serotonergic activity. However, this correlation was present only in males.     

Atorvastatin favorably modulates proinflammatory cytokine profile in patients following deep vein thrombosis

Background

Venous thromboembolism (VTE) has been shown to be associated with inflammation. Statins that might reduce VTE risk have been found to exert anti-inflammatory properties in patients at cardiovascular risk. We sought to investigate whether anti-inflammatory effects of atorvastatin can be observed in VTE patients.

Materials and Methods

Atorvastatin 40 mg/d was given for 3 days to 26 consecutive VTE patients following discontinuation of anticoagulant therapy and 25 controls. We evaluated interleukin (IL)-1b, IL-6, IL-8, IL-10, soluble P-selectin and von Willebrand factor (vWF) antigen in peripheral venous blood.

Results

The VTE patients displayed higher C-reactive protein (p = 0.013), IL-1b (p = 0.03), IL-8 (p = 0.03) and vWF (p < 0.0001) compared with the controls. In VTE patients atorvastatin decreased IL-6 (p = 0.0003), IL-8 (p = 0.003) and P-selectin (p < 0.0001), but increased IL-10 (p = 0.001), with no association with C-reactive protein or cholesterol-lowering effects. Atorvastatin reduced IL-1b (p = 0.01), IL-6 (p = 0.03) and P-selectin (p = 0.002) in controls. Residual venous thrombosis was associated with elevated IL-6 and P-selectin, whereas patients with proximal deep vein thrombosis showed elevated P-selecitn prior to and following statin administration (all p < 0.05).

Conclusion

A 3-day administration of atorvastatin reduces inflammation without decrease in C-reactive protein in VTE patients.     

Coronary thrombi neovascularization in patients with ST-elevation myocardial infarction - clinical and angiographic implications

Introduction

Coronary artery thrombosis in ST-elevation myocardial infarction (STEMI) is a dynamic process often preceded by episodes of silent plaque rupture and subocclusive thrombosis. Thrombus organization is achieved by ingrowth of endothelial and smooth muscle cells. Clinical significance and impact of thrombus neovascularization on primary percutaneous coronary intervention (pPCI) outcome remain unclear. Therefore we investigated composition and neovascularization of thrombi aspirated during pPCI and their association with clinical and angiographic parameters of STEMI patients.

Methods

Aspirated thrombi retrieved from 84 STEMI patients were classified as fresh (< 1 day), lytic (1-5 days) or organized (> 5 days). Thrombus neovascularization was evaluated immunohistochemically using CD34, CD31 and VEGF antibodies. CD34 and CD31 immunopositive (CD34/CD31 +) cells were organized as single, clusters and microvessels. VEGF positivity was graded as low or high, based on thrombus surface immunopositive area.

Results

CD34/CD31 + cells were present in 67% of all aspirated thrombi. Thrombus CD34/CD31 positivity was associated with previous history of angina pectoris (χ² = 6.142, p = 0.013) and lower myocardial blush grade (MBG < 3, χ² = 12.602, p < 0.001). Organization of CD34/CD31 + cells showed inverse association with the extent of VEGF positivity (χ² = 10.607, p = 0.005). Fresh thrombi were associated with shorter ischemic time (U = 237.5, p = 0.002) and MBG 3 (χ² = 6.379, p = 0.012).

Conclusions

Older thrombus age and neovascularization are associated with suboptimal myocardial perfusion in STEMI patients. Thrombus VEGF expression is inversely associated with degree of CD34 + cell organization. Therefore, neovascularization of aspirated thrombi may indicate the duration of thrombosis, coronary microcirculation status and outcome in STEMI patients.     

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

Introduction

Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists.

Patients and methods

Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days.

Results

Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45 ± 17 U) and returned to a normal range (> 84 U) after 6 days (90 ± 26 U; p < 0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p = 0.002) and thrombin receptor-activating peptide-induced (p = 0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up.

Conclusions

Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.     

Do sleep,stress, and illness explain daily variations in fatigue? A prospective study

Objective

Fatigue is related to a number of serious diseases, as well as to general well-being. It is also a major cause of sickness absence and use of health facilities. Still, the determinants of variations in fatigue are little investigated. The purpose of present study was to investigate the relationships between the daily variations of fatigue with sleep during the previous night, stress or disease symptoms during the same day — across 42 consecutive days of normal life.

Methods

50 individuals participated and gave diary reports and used an actigraph across the 42 days. The data was analyzed using a multilevel approach with mixed model regression.

Results

The analyses showed that the day-to-day variation in fatigue was related to (poor) sleep quality (p < .001) and (reduced) sleep duration (p < .01) the previous night, as well as to higher stress (p < .05), and to the occurrence of a cold or fever (p < .001) during the same day as the fatigue rating. Fatigue was also strongly related to poorer subjective health (p < .001) and sleepiness (p < .001) during the same day.

Conclusion

The results indicate that prior sleep (and sleepiness) as well as stress and illness are consistently connected to how fatigue is experienced during normal living conditions.     

Differences in the clinical course of heparin induced thrombocytopenia before and after the availability of HIT IgG class testing

Introduction

To determine whether the HIT IgG class platelet factor 4 (PF4) enzyme immunoabsorbant assay (EIA) influenced the duration of parenteral direct thrombin inhibitor (pDTI) therapy or bleeding risk in patients started on pDTI for a presumed diagnosis of HIT.

Materials/Methods

187 patients started on pDTI for presumed HIT were assessed in two time periods before (period 1, n = 88 patients) and after the introduction of an IgG-specific assay (period 2, n = 99 patients).

Results

Patients in period 2 were treated with pDTI therapy for a median of 5 days less (p < 0.0001) however the incidence of Grade III and IV bleeding episodes was not different. Bleeding was observed to occur early during the hospital course at a median of 2-3 days after initiation of the pDTI. The average pDTI drug acquisition cost was markedly decreased in period 2 when compared to period 1 (p < 0.0001).

Conclusions

Implementation of the IgG class HIT EIA resulted in a decrease in the number of days on a pDTI and a decrease in the average pDTI acquisition cost per patient without an observed change in serious bleeding events.     

CVD risk factors are related to plasma fibrin clot properties independent of total and or γ’ fibrinogen concentration

Introduction

Cardiovascular disease (CVD) risk factors are associated with total fibrinogen concentration and/or altered clot structure. It is however, unclear whether such associations with clot structure are ascribed to fibrinogen concentration or other independent mechanisms. We aimed to determine whether CVD risk factors associated with increased total and/or γ’ fibrinogen concentration, were also associated with altered fibrin clot properties and secondly whether such associations were due to the fibrinogen concentration or through independent associations.

Materials and methods

In a plasma setting CVD risk factors (including total and γ’ fibrinogen concentration) were cross-sectionally analysed in 2010 apparently healthy black South African participants. Kinetics of clot formation (lag time, slope and maximum absorbance) as well as clot lysis times were calculated from turbidity curves.

Results

Of the measured CVD risk factors age, metabolic syndrome, C-reactive protein (CRP), high density lipoprotein (HDL)-cholesterol and homocysteine were significantly associated with altered fibrin clot properties after adjustment for total and or γ’ fibrinogen concentration. Aging was associated with thicker fibres (p = 0.004) while both metabolic syndrome and low HDL-cholesterol levels were associated with lower rates of lateral aggregation (slope), (p = 0.0004 and p = 0.0009), and the formation of thinner fibres (p = 0.007 and p = 0.0004). Elevated CRP was associated with increased rates of lateral aggregation (p = 0.002) and consequently thicker fibres (p < 0.0001). Hyperhomocysteinemia was associated with increased rates of lateral aggregation (p = 0.0007) without affecting fibre thickness.

Conclusion

Final clot structure may contribute to increased CVD risk in vivo through associations with other CVD risk factors independent from total or γ’ fibrinogen concentration.     

Inhibitory effects of LDL-associated tissue factor pathway inhibitor

Introduction

Tissue factor pathway inhibitor (TFPI) is present in plasma as full-length free TFPI (TFPIα) and as C-terminally degraded forms mainly associated with low-density lipoprotein particles (LDL-TFPI). Addition of TFPIα to plasma induces a prolongation of the clotting time when tested in a diluted prothrombin time (dPT) assay, whereas no prolongation is observed with LDL-TFPI or truncated recombinant TFPI (TFPI_1–161). The aim was to further characterize kinetic properties of purified LDL-TFPI in thrombin generation and chromogenic activity assays.

Materials and Methods

LDL-TFPI was purified from human plasma by sequential flotation ultracentrifugation. Thrombin generation was measured in human plasma or in FVIII-immunodepleted plasma using either 1 pM tissue factor and 4 μM phospholipids or 0.5 nM factor Xa (FXa) and 4 μM phospholipids, respectively.

Results

TFPIα prolonged the lag-phase and decreased the thrombin peak in tissue factor-induced thrombin generation, whereas LDL-TFPI exclusively decreased the peak height of thrombin without effecting the lag phase. Steady-state and transient kinetics showed that LDL-TFPI was a more potent inhibitor of FXa than TFPIα and TFPI_1–161, indicating that FXa inhibition was not rate determining for the lag phase, whereas it appeared to affect thrombin generation during the propagation phase. This was supported by FXa-induced thrombin generation showing that LDL-TFPI, compared with TFPIα, more actively decreased the peak height.

Conclusions

Our results suggest that LDL-TFPI affects thrombin generation during the propagation phase, and is kinetically different from TFPI_1–161. It may therefore play a more prominent physiological role in vivo than hereto anticipated from dPT measurements.