Arterial Vascular Events Research Articles

Abstract 203: Outcomes Comparison of Low Risk Medical and Surgical Patients Treated with Unfractionated Heparin vs. Enoxaparin

Objectives: We sought to compare the relative risks for adverse arterial vascular events in patients considered to be low risk for venous thromboembolism (VTE) events who were treated with enoxaparin compared to unfractionated heparin (UFH) for VTE prophylaxis, while comparing clinical efficacy for VTE and overall inpatient costs. Methods: We retrospectively identified patients admitted to the medical and general surgical services who received VTE prophylaxis with either UFH or enoxaparin and compared outcomes before and after implementation of a evidenced based anticoagulation protocol during a twelve month period. Exclusions were: (1) high risk surgical patients, specifically patients undergoing orthopedic, cardiovascular, and bariatric surgery; (2) high risk medical patients, specifically patients admitted with, or having a history of, pulmonary embolism (PE), deep venous thrombosis, atrial fibrillation, or valve replacement; and (3) patients with a therapeutic INR (>2.0) on admission. Using Logistic regression analysis, the following outcomes were compared between the UFH and enoxaparin treated groups: deep venous thrombosis, PE, myocardial infarction (MI), stroke, transient ischemic attack (TIA), heparin induced thrombocytopenia (HIT) and mortality among both groups. Length of hospital stay (LOS) and length of intensive care unit (ICU) LOS were compared using multiple regression analysis. Total costs between the two treatment groups were also compared using a t-test. Results: From the study group, a total of 6,390 patients received UFH prophylaxis and 1,565 received enoxaparin. The enoxaparin patients’ average age was younger than the UFH treated patients’ age by 2.4 years (59.1 and 61.5 years old, respectively, p<0.0001). The incidence of deep venous thrombosis, PE and HIT was similar in both groups. The enoxaparin group had a 52% higher odds for TIA (3.64 vs. 2.49 per 100 patients, OR=1.52, CI 1.113,2.078, p= 0.0024), 61% higher odds for stroke (9.3 vs. 6.6 per 100 patients, OR=1.589, CI 1.298, 1.945, p= 0.0009), while having a 54% lower odds for MI (2.1 vs. 4.7 per 100 patients, OR=0.46,CI 0.32, 0.66, p<0.0001) and lower mortality rate (0 vs. 1.3 per 100 patients). The hospital LOS in the enoxaparin group was 0.73 days lower than in the heparin group (4.41 days vs. 5.13 days, p<0.0001) and the ICU LOS was also shorter by 0.6 days (0.095 vs. 0.69 days, p<0.0001). The total cost (20, 690 vs. 25,946 dollars) was lower in the enoxaparin group. Conclusions: In low-risk medical and general surgical patients, UFH was as effective as enoxaparin in the prevention of thromboembolic events, with no difference in the incidence of HIT. When compared to UFH, enoxaparin was associated with lower MI and mortality rates, and shorter LOS and ICU LOS, at the expense of higher rates of stroke and TIA. Enoxaparin was associated with lower total inpatient costs than UFH.

Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in chronic myeloid leukemia: a single institution study

Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in chronic myeloid leukemia: a single institution study

Risk factors for vascular occlusive events and death due to bleeding in trauma patients; an analysis of the CRASH-2 cohort.

BackgroundVascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding.Methods and FindingsWe conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001).ConclusionsPatients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.

Acute Renal Infarction

Renal infarction is an arterial vascular event that may cause irreversible damage to kidney tissues. This study describes the clinical characteristics of patients with renal infarction according to underlying mechanism of vascular injury. This study retrospectively identified 94 patients with renal infarction diagnosed between 1989 and 2011 with the aim of highlighting potential correlations between demographic, clinical, and biologic characteristics and the etiology of renal infarction. Four groups were identified: renal infarction of cardiac origin (cardiac group, n=23), renal infarction associated with renal artery injury (renal injury group, n=29), renal infarction associated with hypercoagulability disorders (hypercoagulable group, n=15), and apparently idiopathic renal infarction (idiopathic group, n=27). Clinical symptoms included abdominal and/or flank pain in 96.8% of cases; 46 patients had uncontrolled hypertension at diagnosis. Laboratory findings included increase of lactate dehydrogenase level (90.5%), increase in C-reactive protein level (77.6%), and renal impairment (40.4%). Compared with renal injury group patients, this study found that cardiac group patients were older (relative risk for 1 year increase=1.21, P=0.001) and displayed a lower diastolic BP (relative risk per 1 mmHg=0.94, P=0.05). Patients in the hypercoagulable group had a significantly lower diastolic BP (relative risk=0.86, P=0.005). Patients in the idiopathic group were older (relative risk=1.13, P=0.01) and less frequently men (relative risk=0.11, P=0.02). Seven patients required hemodialysis at the first evaluation, and zero patients died during the first 30 days. This study suggests that the clinical and biologic characteristics of patients can provide valuable information about the causal mechanism involved in renal infarction occurrence.

Associations of ankle-brachial index (ABI) with cerebral arterial disease and vascular events following ischemic stroke

ObjectivesLow ankle-brachial index (ABI), indicative of peripheral arterial disease (PAD), is a risk factor for stroke. ABI has been shown to be associated with cerebral arterial disease and prognosis following stroke. We studied the associations of the degree of ABI lowering with extracranial carotid disease (ECD), intracranial large artery disease (ICLAD), and subsequent vascular events in a prospective cohort of acute ischemic stroke patients. MethodsABI, extracranial and intracranial cerebral arteries were assessed in a blinded manner. ABI was categorized into 0.9–1.3 (normal), 0.8–0.89 (mildly lowered) and <0.8 (severely lowered). Follow-up data at 1 year were obtained from standardized telephone interviews and verified with medical records. ResultsAmong the 1311 patients, 73% had normal ABI, 13% had ABI 0.8–0.89 and 13% had ABI <0.8. Compared to patients with normal ABI, those with ABI<0.8 had higher prevalence of severe ECD (15% vs. 5%, p = 0.006) and ICLAD (72% vs. 48%, p = 0.003), even after adjustment for age, gender, hypertension, diabetes, hyperlipidemia, smoking, ischemic heart disease and atrial fibrillation (severe ECD p < 0.001, ICLAD p < 0.001). At 1 year, patients with ABI <0.8 had a higher incidence of composite vascular events (19% vs. 11%, p = 0.02), stroke (15% vs. 10%, p = 0.06) and myocardial infarction (4% vs. 2%, p = 0.07) than patients with normal ABI. ConclusionAmong ischemic stroke patients, large cerebral arterial disease and incidence of subsequent vascular events at 1 year were associated with severe ABI lowering <0.8, but not with mild ABI lowering (0.8–0.89).

Evaluation of Clinical Outcomes and Renal Vascular Pathology among Patients with Lupus

The objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis. Renal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality. Biopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m(2), P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power. Renal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events.

Association of autoantibodies to heat‐shock protein 60 with arterial vascular events in patients with antiphospholipid antibodies

Anti-heat shock protein 60 autoantibodies (anti-Hsp60) are associated with cardiovascular disease and are known to affect endothelial cells in vitro, and we have recently shown that anti-Hsp60 promote thrombosis in a murine model of arterial injury. Based on those findings, we undertook the present study to investigate the hypothesis that the presence of anti-Hsp60, alone or in combination with other thrombogenic risk factors, is associated with an elevated risk of vascular events. The study population was derived from 3 ongoing cohort studies: 2 independent systemic lupus erythematosus (SLE) registries and 1 cohort comprising SLE patients and non-SLE patients. Data from a total of 402 participants were captured; 199 of these participants had had confirmed vascular events (arterial vascular events in 102, venous vascular events in 76, and both arterial and venous vascular events in 21). Anti-Hsp60 were detected by enzyme-linked immunoassay, and association with vascular events was assessed by regression analysis. Multiple regression analysis revealed that arterial vascular events were associated with male sex, age, and hypertension. Analyses of the vascular events according to their origin showed an association of anti-Hsp60 with arterial vascular events (odds ratio 2.26 [95% confidence interval 1.13-4.52]), but not with venous vascular events. Anti-Hsp60 increased the risk of arterial vascular events (odds ratio 5.54 [95% confidence interval 1.89-16.25]) in antiphospholipid antibody (aPL)-positive, but not aPL-negative, individuals. We demonstrate that anti-Hsp60 are associated with an increased risk of arterial vascular events, but not venous vascular events, in aPL-positive individuals. These data suggest that anti-Hsp60 may serve as a useful biomarker to distinguish risk of arterial and venous vascular events in patients with aPL.

Hormone Therapy Administration in Postmenopausal Women and Risk of Stroke

HRT, consisting of estrogens alone, or in combination with a progestogen, is widely used for the relief of symptoms in postmenopausal women. Early observational studies have suggested that HRT might be associated with a reduced risk of cardio- and cerebro-vascular events. These encouraging results prompted randomized controlled trials assessing the risks and benefits of HRT in primary and secondary prevention of arterial vascular events. However, these clinical trials and further observational studies did not confirm the protective effect of HRT; it is now established that HRT increases the risk of stroke. This increased risk is mainly related to an increased risk of ischemic stroke. Oral estrogen alone and combined with progestogen are associated with a similar increased risk, which may be dose dependent. Conversely, a low dose of transdermal estrogens with or without a progestogen does not seem to be associated with such an increased risk of stroke, whereas the impact of tibolone, a synthetic steroid, remains uncertain. In summary, there is now a large amount of evidence demonstrating that HRT is associated with increased risk of stroke, in particular, ischemic subtype.

Diabetes Mellitus and Cardiovascular Prevention: The Role and the Limitations of Currently Available Antiplatelet Drugs

Diabetes mellitus (DM) is associated with macrovascular and microvascular complications. Platelets have a “key role” in atherogenesis and its thrombotic complications in subjects with DM. Moreover, the concomitant presence of multiple “classical” cardiovascular risk factors in diabetic subjects contributes to enhanced atherothrombotic risk. Antiplatelet agents are effective in primary and secondary prevention of arterial thrombosis (cardiovascular events, ischaemic stroke, and peripheral arterial occlusive disease). The role of chronic administration of antiplatelet drugs in primary prevention of arterial vascular events is known to be less clear than in secondary prevention, and, also in diabetic patients, the decision to give primary prophylaxis should be taken on an individual-patient basis, after a careful evaluation of the balance between the expected benefits and the risk of major bleedings. Although, currently, treatment has proven useful in reducing vascular events, diabetic patients continue to have a higher risk of adverse cardiovascular events compared with those in nondiabetic patients. This paper reviews the role of currently available antiplatelet drugs in primary and secondary prevention of vascular events in diabetic patients and the limitations of these drugs, and it discusses the role of novel and more potent antiplatelets and of new agents currently under clinical development.

Glomerular filtration rate predicts arterial events in women with systemic lupus erythematosus

To determine whether renal function predicts the development of cardiovascular disease and other arterial vascular events in patients with SLE. An inception cohort of 437 females was studied. Baseline estimated glomerular filtration rate (eGFR) was calculated using serum creatinine and the abbreviated Modification of Diet in Renal Disease Study Group formula. Arterial events including myocardial infarction, angina, transient ischaemic attacks, cerebral vascular accidents and other arterial events were documented at up to 15 years since the first visit. Disease activity was determined using SLEDAI. Patients were classified into those with or without arterial events and further into events that occurred within or after 3 years since the first visit (events <3 years, events ≥3 years). The association between eGFR and risks of arterial events was investigated using the Cox proportional hazards model. There was a total of 58 arterial events of which 51.9% were events ≥ 3 years. Patients with arterial events had a significantly lower baseline eGFR and were significantly older than those without arterial events. Furthermore, baseline eGFR was significantly lower in events <3 years compared with events ≥ 3 years. Baseline eGFR, age and baseline SLEDAI were significantly associated with the risks of arterial events [eGFR: hazard ratio (HR) = 0.986; age: HR = 1.032; SLEDAI: HR = 1.041]. Lower baseline eGFR, older age and higher SLEDAI score were significantly associated with increasing odds of developing arterial events at an earlier stage of SLE.

Advances in gout: some answers, more questions

In a previous issue of the journal, Becker and colleagues present efficacy and safety data from a large study comparing febuxostat to allopurinol. The study showed non-inferiority of febuxostat 40 mg/day in lowering serum urate compared to allopurinol 200 to 300 mg/day. More importantly, the study showed a similar frequency of important cardiovascular adverse events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) for febuxostat 40 mg/day (0%), febuxostat 80 mg/day (0.4%) and allopurinol groups (0.4%). Other cardiac adverse event rates (unstable angina, coronary revascularization, cerebral revascularization, transient ischemic attack, venous and peripheral arterial vascular thrombotic event, congestive heart failure, and arrhythmia) were also similar for febuxostat 40 mg/day (1.3%), febuxostat 80 mg/day (1.2%) and allopurinol groups (0.9%). A meta-analysis of safety data from published studies is presented.

Factors Associated with Arterial Vascular Events in PROFILE: A Multiethnic Lupus Cohort

The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised SLE patients (n = 1333) of defined ethnicity from five different US institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene. Patient characteristics were analyzed by univariable and multivariable Cox proportional hazards regression analyses. One-hundred twenty-three (9.8%) patients had at least one incident arterial event. Age at cohort enrollment (HR = 1.04, 95% CI 1.03-1.06), smoking (HR = 2.20, 95% CI 1.40-3.46) and the CRP2* C alleles (HR = 1.91, 95% CI 1.04-3.49) were associated with a shorter time-to-the occurrence of arterial vascular events. Some clinical manifestations of disease activity were associated with a shorter time-to-occurrence [psychosis (HR = 2.21, 95% CI 1.10-4.44), seizures (HR = 1.85, 95% CI 1.00-3.24) and anaemia (HR = 1.83, 95% CI 1.02-3.31)], but others were not [arthritis (HR = 0.32, 95% CI 0.18-0.58)]. In conclusion, older patients, especially in the context of a predisposing environmental factor (smoking) and severe clinical manifestations, are at higher risk of having arterial vascular events. The genetic contribution of the variation at the CRP locus was not obscured by demographic or clinical variables. Awareness of these factors should lead to more effective management strategies of patients at risk for arterial vascular events.

Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

A new systematic review regarding this contested women's health issue is certainly welcome.1 However, the inclusion of several trials evaluating the effects of menopausal hormone therapies (MHTs) on coronary heart disease (CHD), myocardial infarction, cerebrovascular events, and venous thrombo-embolism events ( Figure 3 )1 is debatable. …

Association of killer cell immunoglobulin–like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus

To determine whether killer cell immunologlobulin-like receptor (KIR) genotypes are associated with vasculitis, vascular arterial events or anticardiolipin (aCL) antibodies in patients with lupus. A total of 304 patients followed prospectively at the University of Toronto Lupus Clinic were assessed for the occurrence of vasculitis and vascular arterial events. Molecular HLA-C and KIR (presence or absence of KIR2DL1, 2DL2, 2DL3, 2DS1 and 2DS2) genotyping were performed. Chi-square and logistic regression were used to analyse association between KIR genes and vascular arterial events and aCL antibodies. In patients with vascular arterial events, there was a significant increase in KIR2DS2 (60% vs 45%, P = 0.02) and in KIR2DL2 (62% vs 47%, P = 0.01) compared with patients without events. There was no increase in activating KIR genotypes in patients with vasculitis. In patients with aCL antibodies, significant increases were seen in KIR2DS2 (54% vs 41%, P = 0.03) and KIR2DL2 (58% vs 41%, P = 0.003), but KIR2DL3 was decreased (87% vs 95%, P = 0.03). Logistic regression confirmed independent association of KIR2DS2 with vascular arterial events. We found an increase in KIR2DS2 in lupus patients with vascular arterial events, but not in patients with vasculitis.

Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

AimsRandomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear.Methods and resultsRCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14–1.53) and VTE (OR 2.05, 95% CI 1.44–2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90–1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12–1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE.ConclusionHRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.

Systemic Lupus Erythematosus in a Multiethnic US Cohort (LUMINA L II)

To examine the influence of hormone replacement therapy (HRT) in the occurrence of vascular arterial and venous thrombotic events in postmenopausal women with systemic lupus erythematosus (SLE). SLE women aged > or =16 years, disease duration < or =5 years from LUMINA, a multiethnic, longitudinal outcome study, were included. Menopause was defined at disease onset as the presence of amenorrhea >6 months and/or oophorectomy, and/or increased follicle stimulating hormone values, and/or HRT use regardless of the presence or absence of climacteric symptoms (hot flashes). Patients were divided into HRT ever users and nonusers. Patients with positive antiphospholipid antibodies (n = 9) or vascular arterial events (n = 1) occurring before HRT use were excluded. The occurrence of vascular arterial and venous thrombotic events was compared between HRT users and HRT nonusers and its role examined by logistic regression after adjusting for "confounding by indication" using propensity score or logistic regression analyses. Seventy-two postmenopausal women, 32 (44%) HRT users and 40 (56%) HRT nonusers, were studied. HRT use was associated with fewer vascular arterial but not venous thrombotic events (P = 0.021) in the univariable analyses. However, after adjusting for the propensity score, HRT use was no longer significant (P = 0.064). Comparable results were obtained by logistic regression. HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but our data suggest its use may be safe if antiphospholipid antibodies are not present or vascular arterial events have not previously occurred.

Erythema nodosum secondary to aromatase inhibitor use in breast cancer patients: case reports and review of the literature

Aromatase inhibitors (AI's) are increasingly being incorporated in the treatment strategy for hormone receptor positive breast cancer either alone or in combination with chemotherapy, biologics in both the adjuvant and metastatic setting [1]. They markedly suppress plasma estrogen levels by inhibiting or inactivating aromatase, the enzyme responsible for the synthesis of estrogens from androgenic substrates [1]. Currently, the three selective aromatase inhibitors that are available are anastrozole, letrozole and exemestane which reduce circulating estrogen to 1 to 10% of pretreatment levels [2]. For advanced breast cancer, aromatase inhibitors appear to be at a minimum, equivalent and perhaps even better than tamoxifen in the first line setting [3, 4]. In primary breast cancer, adjuvant therapy with anastrozole or letrozole appears to be superior to tamoxifen in reducing the risk of relapse [5, 6]. Common adverse effects associated with AI's include arthralgias (21%), myalgias (12%), other musculoskeletal disorders (28%) and an up to 60% increased risk of bone fracture [7, 8]. However, anastrozole, exemestane and letrozole are associated with significantly fewer endometrial cancers, as well as venous and arterial vascular events, when compared with tamoxifen [9, 10]. Very rarely letrozole and anastrozole can cause a skin rash; the frequency of its occurrence has not been quantified(. )However, exemestane has not been reported to cause a skin rash [11]. To date, erythema nodosum (EN) has not been reported as a dermatologic side effect of AI's. Here, we report three cases of EN which developed in postmenopausal breast cancer patients on AI's.

Absolute annual incidences of first events of venous thromboembolism and arterial vascular events in individuals with elevated FVIII:c

Elevated levels of factor VIII:c (elevated FVIII:c) are associated with an increased risk for venous thromboembolism (VTE) and arterial vascular events, and are at least in part determined genetically. We prospectively followed 192 asymptomatic individuals with elevated FVIII:c (>150%) and 340 with normal levels for an average duration of 31 months (range 7 to 56 months) to investigate the risk of VTE and arterial vascular events. Participants were first degree relatives of consecutive patients with elevated FVIII:c and VTE or arterial vascular events before the age of 50 years. The incidences of VTE were 1.25% (0.46-2.73) per year in the subjects with elevated FVIII:c, versus 0.23% (0.03-0.82) in those with normal levels (OR 5.5 [1.1-27.3]). The annual incidences of arterial vascular events were 1.04% (0.34-2.42) and 0.23% (0.03-0.82) in relatives with and without elevated levels of FVIII:c, respectively (OR: 4.5 [0.9-23.5]). After adjustment for age, smoking, known diabetes mellitus, hyperlipidemia, and hypertension, the odds ratio for any event was 3.7 (1.1-13.1). In conclusion, asymptomatic individuals with elevated FVIII:c levels and a positive family history of VTE or arterial vascular events before the age of 50 appear to have a high annual incidence of first VTE and arterial vascular events. Elevated FVIII:c may be a common risk factor for both clinical entities.

Effects of hormone treatment on hemostasis variables

A survey was made of the changes in hemostasis and related inflammatory biomarkers for hormone treatments (HT) of women. Treatments included were oral and non-oral estrogens combined or not with progestogens, raloxifene, tamoxifene, tibolone and ethinylestradiol in oral contraceptives with non-androgenic progestogens.Special attention was given to dosages lower than the present standard dose and we explored how treatment variants approached a situation of minimal changes in biomarkers.For oral unopposed estrogens, dose reduction effectively reduced the changes in some hemostasis markers, but not in a specific set of anticoagulant variables (antithrombin, protein S, tissue factor pathway inhibitor, and the endogenous thrombin potential assay for resistance to activated protein C). Inflammation markers from the liver showed a dose-dependent reduction but effects were not nullified at the lowest dose tested. It was concluded that adequate reduction of estrogen dose for these effects will coincide with the dose-range of efficacy.Androgenic progestogens may be suitable for further reducing the impact of estrogens on some of the anticoagulant variables; reductions of estrogen-induced C-reactive protein increases appear possible with specific progestogens (medroxyprogesterone actate, nomegestrol acetate).For non-oral unopposed estrogens, all variables except inflammation biomarkers from the vascular wall showed minimal changes. Reduction in vascular inflammatory biomarkers, considered to mark anti-inflammatory effects, is augmented by medroxyprogesterone actate or norethisterone acetate.It was concluded that unopposed, non-oral estrogen treatment is the present best available option approaching minimal effects of treatment on biomarkers. Progestogen selection requires more data.We postulated that minimal effects on all cardiovascular biomarkers should define the HT with maximal safety for venous and arterial vascular events. The survey has identified specific biomarkers sensitive to low-dose unopposed and opposed estrogen which can be used to characterize future preparations for HT.

Inflammation and Coagulation in the Cardiovascular System

See related article, pages 1261–1269 We need to know more about the functional interplay between the coagulation or fibrinolytic pathways and acute inflammation in the vasculature, especially from the viewpoint of acute infections and sepsis. This is a concept that is relevant in both the macro- and microvasculature. An especially important clinical infection is influenza. The extent to which endemic or epidemic influenza elicits systemic inflammation and coagulation is an evolving story. In this issue of the journal, Keller et al provide a focused dissection of changes in coagulation and fibrinolysis parameters in a murine model of respiratory influenza.1 Their findings give us reason to remind ourselves about the important pathways involved. Traditional and nontraditional Framingham risk factors for accelerated atherosclerosis, such as genetic susceptibility alleles or lifestyle issues, provide a background for the acute and chronic infectious diseases that are superimposed on the daily lives of patients. How these exogenous pathogens contribute to disease progression has stimulated much discussion but limited insight. This may be because of, in part, the difficulties in studying these in vivo concepts in patients. Scholarly clinical epidemiology studies have provided support for the view that acute infections are chronologically associated with an acute but transient risk for stroke and myocardial infarction. Arguments continue for a contribution of intralesional pathogens. However, it is more increasingly appreciated that acute infections are associated with systemic inflammation that increases the risk for superimposed acute arterial vascular events.2,3 Parallel concepts have emerged for the venous side of the circulation.4,5 Smeeth et al report that venous thromboembolic disease is also acutely increased in the community after acute infections.5 But which type of infections are relevant? The evidence for acute respiratory tract and urinary tract …