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      Risk marker associations with venous thrombotic events: a cross-sectional analysis

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          Abstract

          Objective

          To examine the interrelations among, and risk marker associations for, superficial and deep venous events—superficial venous thrombosis (SVT), deep venous thrombosis (DVT) and pulmonary embolism (PE).

          Design

          Cross-sectional analysis.

          Setting

          San Diego, California, USA.

          Participants

          2404 men and women aged 40–79 years from four ethnic groups: non-Hispanic White, Hispanic, African-American and Asian. The study sample was drawn from current and former staff and employees of the University of California, San Diego and their spouses/significant others.

          Outcome measures

          Superficial and deep venous events, specifically SVT, DVT, PE and combined deep venous events (DVE) comprising DVT and PE.

          Results

          Significant correlates on multivariable analysis were, for SVT: female sex, ethnicity (African-American=protective), lower educational attainment, immobility and family history of varicose veins. For DVT and DVE, significant correlates included: heavy smoking, immobility and family history of DVEs (borderline for DVE). For PE, significant predictors included immobility and, in contrast to DVT, blood pressure (BP, systolic or diastolic). In women, oestrogen use duration for hormone replacement therapy, in all and among oestrogen users, predicted PE and DVE, respectively.

          Conclusions

          These findings fortify evidence for known risk correlates/predictors for venous disease, such as family history, hormone use and immobility. New risk associations are shown. Striking among these is an association of PE, but not DVT, to elevated BP: we conjecture PE may serve as cause rather than consequence. Future studies should evaluate the temporal direction of this association. Oxidative stress and cell energy compromise are proposed to explain and predict many risk factors, operating through cell-death mediated triggering of coagulation activation.

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          Most cited references69

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          Epidemiology of cancer-associated venous thrombosis.

          Cancer-associated venous thrombosis is a common condition, although the reported incidence varies widely between studies depending on patient population, start and duration of follow-up, and the method of detecting and reporting thrombotic events. Furthermore, as cancer is a heterogeneous disease, the risk of venous thrombosis depends on cancer types and stages, treatment measures, and patient-related factors. In general, cancer patients with venous thrombosis do not fare well and have an increased mortality compared with cancer patients without. This may be explained by the more aggressive type of malignancies associated with this condition. It is hypothesized that thromboprophylaxis in cancer patients might improve prognosis and quality of life by preventing thrombotic events. However, anticoagulant treatment leads to increased bleeding, particularly in this patient group, so in case of proven benefit of thromboprophylaxis, only patients with a high risk of venous thrombosis should be considered. This review describes the literature on incidence of and risk factors for cancer-associated venous thrombosis, with the aim to provide a basis for identification of high-risk patients and for further development and refinement of prediction models. Furthermore, knowledge on risk factors for cancer-related venous thrombosis may enhance the understanding of the pathophysiology of thrombosis in these patients.
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            Alcohol, Oxidative Stress, and Free Radical Damage

            Reactive oxygen species (ROS) are small, highly reactive, oxygen-containing molecules that are naturally generated in small amounts during the body’s metabolic reactions and can react with and damage complex cellular molecules such as fats, proteins, or DNA. Alcohol promotes the generation of ROS and/or interferes with the body’s normal defense mechanisms against these compounds through numerous processes, particularly in the liver. For example, alcohol breakdown in the liver results in the formation of molecules whose further metabolism in the cell leads to ROS production. Alcohol also stimulates the activity of enzymes called cytochrome P450s, which contribute to ROS production. Further, alcohol can alter the levels of certain metals in the body, thereby facilitating ROS production. Finally, alcohol reduces the levels of agents that can eliminate ROS (i.e., antioxidants). The resulting state of the cell, known as oxidative stress, can lead to cell injury. ROS production and oxidative stress in liver cells play a central role in the development of alcoholic liver disease.
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              Alcohol-induced oxidative stress.

              Alcohol-induced oxidative stress is linked to the metabolism of ethanol involving both microsomal and mitochondrial systems. Ethanol metabolism is directly involved in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These form an environment favourable to oxidative stress. Ethanol treatment results in the depletion of GSH levels and decreases antioxidant activity. It elevates malondialdehyde (MDA), hydroxyethyl radical (HER), and hydroxynonenal (HNE) protein adducts. These cause the modification of all biological structures and consequently result in serious malfunction of cells and tissues.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2014
                21 March 2014
                : 4
                : 3
                : e003208
                Affiliations
                [1 ]Department of Medicine, University of California San Diego , La Jolla, California, USA
                [2 ]Department of Family and Preventive Medicine, University of California San Diego , La Jolla, California, USA
                [3 ]Internal Medicine, Scripps Green Hospital , La Jolla, California, USA
                Author notes
                [Correspondence to ] Beatrice A Golomb; bgolomb@ 123456ucsd.edu

                BAG and VTC shared first authorship.

                Article
                bmjopen-2013-003208
                10.1136/bmjopen-2013-003208
                3963072
                eeb1a8b8-06a0-435c-aaf3-9af4e4d983f4
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 7 June 2013
                : 8 November 2013
                : 11 November 2013
                Categories
                1506
                1692
                Epidemiology
                Research

                Medicine
                Medicine

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