Pulmonary thromboembolism (PTE) is a life-threatening disease which always presents in patients with deep vein thrombosis (DVT). There are few statements in guidelines regarding indications for anticoagulation based on the location of DVT. We investigated whether the relative risk of PTE depends on thrombus location and bleeding complications with anticoagulation therapy. Between January 1 and July 10, 2007, 461 patients underwent lower extremity venous ultrasound studies, and 129 patients were diagnosed as DVT (60 males, 66.9 ± 13.3 years). We retrospectively studied the incidence of PTE and bleeding complications associated with anticoagulation therapy. Average follow-up period was 536 ± 324 days. Above and below knee thrombosis was present in 60 and 69 patients, respectively. Warfarin was administered in 60 patients. Nine patients developed PTE. Multivariate analysis showed the absence of anticoagulation therapy and location of DVT (above knee) to be significantly correlated with onset of PTE (anticoagulation; P < 0.01, location; P = 0.02). However, the incidence of bleeding was not significantly different between above knee and below knee vein thrombosis (P = 0.72). In conclusion, below knee vein thrombosis carries a relatively low risk of PTE, but the incidence of bleeding complications does not depend on thrombosis location. This suggests that the indication of anticoagulation therapy should be based on DVT location.

Central obesity is a key feature of the metabolic syndrome (metS), a multiplex risk factor for subsequent development of type 2 diabetes and cardiovascular disease. Many metabolic alterations closely related to this condition exert effects on platelets and vascular cells. A procoagulant and hypofibrinolytic state has been identified, mainly underlain by inflammation, oxidative stress, dyslipidaemia, and ectopic fat that accompany central obesity. In support of these data, central obesity independently predisposes not only to atherothrombosis but also to venous thrombosis.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and its life-threatening complication, pulmonary embolism (PE), are among the most frequent causes of morbidity and mortality in developed countries. In the United States alone, the number of deaths due to VTE approaches 300,000 annually [1]. Blood flow restriction or stasis is considered a major factor driving DVT [2]. Regardless of its initial cause (bed-ridden position, long-haul flights, limb paralysis, etc.), delayed blood renewal in stasis is believed to produce limited oxygen supply to the vein walls (hypoxia), especially in the valvular sinus, which triggers thrombus development [2]. This article is protected by copyright. All rights reserved.

Background:

Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events. We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin (Hb) irrespective of treatment target and randomized allocation.

Methods:

We performed a post hoc analysis from the CHOIR trial. Inclusion criteria were Hb <11.0 g/dl and estimated glomerular filtration rates of 15-50 ml/min/1.73 m(2). To be included in the present analysis, subjects needed to be free of the composite event at 4 months, receive epoetin-alfa, and have ≥1 postbaseline Hb measurement. The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable, while the achieved Hb at month 4 was the confounder representing the subject's underlying response to treatment. The primary outcome was the composite of death, heart failure hospitalization, stroke, or myocardial infarction. A Cox proportional hazard regression model was used in time-to-event analysis.

Results:

Among 1,244 subjects with complete data, the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure. Cox proportional hazard analysis found that those in the middle tertile of Hb achieved (>11.5 to <12.7 g/dl) and the lowest tertile of epoetin-alfa dose exposure level (<5,164 units/week) had the lowest risk. Irrespective of Hb achieved, the relative risk in the highest tertile (>10,095 units/week) of epoetin-alfa dose exposure level was significantly escalated (hazard ratios ranged from 2.536 to 3.572, p < 0.05, when compared to the group of middle Hb tertile and lowered dose tertile). In a multivariable model that adjusted for achieved Hb, albumin, cholesterol, age, prior heart failure, prior stroke, prior deep venous thrombosis, atrial fibrillation or malignancy, the average weekly dose had a significant (p = 0.005) relative risk of 1.067 per 1,000 units of epoetin-alfa for the primary end point.

Conclusions:

In the CHOIR trial, average epoetin-alfa doses >10,095 units/week were associated with increased risks for cardiovascular events irrespective of the Hb achieved within the first 4 months of treatment. These data suggest the weekly epoetin-alfa dose and not the Hb achieved was a principal determinant in the primary outcome observed implicating a cardiovascular toxicity of this erythrocyte-stimulating agent.

Hyperhomocysteinemia is a rare condition which predisposes to atherothrombosis. Recurrent venous thromboembolism (VTE) with hyperhomocysteinemia is known but extremely uncommon. Homocysteine levels of more than 22 umol/L can predispose to VTE in a middle-aged women. We describe a case of a middle-aged woman, community ambulant with recurrent VTE with intermediately high homocysteine levels. She had no other risk factors for recurrent venous thrombosis. In our article, we also discuss hyperhomocysteinemia and its link to VTE.

THIS PAPER REVIEW SEASONAL PATTERNS ACROSS TWELVE CARDIOVASCULAR DISEASES: Deep venous thrombosis, pulmonary embolism, aortic dissection and rupture, stroke, intracerebral hemorrhage, hypertension, heart failure, angina pectoris, myocardial infarction, sudden cardiac death, venricular arrythmia and atrial fibrillation, and discuss a possible cause of the occurrence of these diseases. There is a clear seasonal trend of cardiovascular diseases, with the highest incidence occurring during the colder winter months, which have been described in many countries. This phenomenon likely contributes to the numbers of deaths occurring in winter. The implications of this finding are important for testing the relative importance of the proposed mechanisms. Understanding the influence of season and other factors is essential when seeking to implement effective public health measures.

Hormonal contraception in the form of combined oral contraceptive pills is the most widely used reversible form of contraception in the US. Oral contraceptive (OC) pills have long been associated with risk of venous thromboembolism (VT) and arterial thrombosis (AT). There are more recent publications on risk of venous thromboembolism than arterial thrombosis. Many of the studies on AT have been contradictory in terms of results. The Danish cohort study is the largest study to date on the risk of AT in users of oral contraceptive pills. The study suggests that a lower estrogen dose may be better for preventing myocardial infarction and possibly thrombotic stroke but there is no significant difference according to progestin type for risk of thrombotic stroke or myocardial infarction. It challenges results of previous studies that show incremental risk of arterial thrombosis with smoking. The absolute and relative risks of arterial thrombosis in Danish women who used hormonal contraception were shown to be low. VT is more common than AT in women of reproductive age but AT is associated with a higher risk of mortality and disability. The decision to use hormonal contraceptives and the choice of formulation should be individualized based on patient's age and known risk factors for both VT and AT.

Statins have dramatically improved the treatment of hyperlipidemia and cardiovascular disease through its inhibition of hydroxymethylglutaryl-coenzyme A reductase. While its main effect has long been known, much is yet to be understood about the wide and varied pleiotrophic properties of statins. Some studies have demonstrated that statins contain anti-platelet, anti-thrombotic, anti-inflammatory, cardioprotective, and neuroprotective properties independent of their ability to lower plasma low-density lipoprotein cholesterol. More recently statins have been used in novel ways in the treatment of Alzheimer's disease, sepsis, pneumonia, and bacteremia. In 2000 it was first suggested that statins could decrease the incidence of venous thrombo-embolisms (VTEs). A recent publication showed that not only do statins lower the incidence of deep vein thrombosis and pulmonary embolisms, they do so in a dose-dependent manner. While there is certainly strong evidence demonstrating that statins do indeed lower VTEs, the mechanism is not understood. Possible hypotheses include their anti-inflammatory and anti-thrombotic properties. With only one randomized clinical trial available, further studies must be conducted before routinely recommending statins for prophylaxis of VTEs.