VENOUS THROMBOEMBOLISM AND CORONARY ARTERY DISEASE: IS THERE A LINK?

Transcription

1 VENOUS THROMBOEMBOLISM AND CORONARY ARTERY DISEASE: IS THERE A LINK? Ayman El-Menyar (1), MD, Hassan Al-Thani (2),MD (1)Clinical Research Consultant, (2) Head of Vascular Surgery, Hamad General Hospital & (1)Weill Cornell Medical college, Doha, Qatar

2 Introduction Few studies suggested that some cardiovascular risk factors may be involved in the pathogenesis of Venous Thromboembolism (VTE). The potential association between VTE, atherosclerosis, and atherothrombosis could have clinical implications with respect to screening, risk factor modification, and future therapy.

3 Arterial thrombi tend to occur at places where plaques are formed and shear stress is high>>> platelet-rich White thrombi. In contrast, in VTE, thrombi tend to occur at sites where the vein wall is undamaged and shear stress are low>>> red cell-rich Red thrombi. (>>>treatment is different). A meta-analysis showed that 4% of patients with myocardial infarction had symptomatic pulmonary embolism within 2 weeks post admission. Semin Thromb Hemost Nov;37(8): doi: /s

4 A large retrospective study reported that after a first episode of VTE, there was a 2 to 3-fold increased risk of MI or ischemic stroke mainly in the first year F/U. Data showed a 1.9-fold (95% CI, ) increased risk of arterial thrombosis after venous thrombosis. Semin Thromb Hemost Nov;37(8): doi: /s

5 Herein, We evaluated the association and impact of Venous Thromboembolism in terms of deep vein thrombosis (DVT), pulmonary embolism (PE) and coronary artery disease (CAD).

6 Methods A retrospective cohort study was conducted for all patients presented with clinically suspected DVT and underwent serial Doppler ultrasonography between January 2008 and December 2012, with one year follow-up. Data were collected for the patient demographics, baseline characteristics, predisposing factors, cardiovascular risk factors, laboratory investigations, radiological findings, DVT recurrence, treatment, hospital course, pulmonary embolism (PE), complications and outcome.

7 VTE in our study was diagnosed based on clinical characteristics, laboratory findings and color Doppler ultrasonography. Patients were divided into two groups (group1: no CAD vs. group 2: with CAD). Statistical analysis Data were reported as percentage, mean (± standard deviation), median and range, when applicable. Comparison of variables such as baseline characteristics, risk factors, diagnostic testing, complications and outcome was performed for cases with CAD versus no-cad.

8 Results During the study period 6420 patients were investigated for DVT. DVT was confirmed in 10.3% patients. Medical records that documented the CAD status showed that 65 patients (10.5%) had CAD: In the CAD group, there were 16 patients had myocardial infarction (3.2%) 11 patients had abnormal coagulation profiles in terms of protein C (n=2), protein S (n=3), antithrombin III (n=2) deficiency, hyperhomocysteinemia (n=3), and factor V leiden (n=1).

9 There was higher proportion of CAD among those with left LL DVT in comparison to Right or both LL (p=0.01) There were higher rates of diabetes and hypertension in the CAD group (P=0.001). Recurrent DVT and PE were found in 11 and 3 cases, respectively in the CAD group.

10 The frequency of the prescribed medications were higher in the CAD group in terms of aspirin, clopidogrel, and heparin (p=0.001), whereas Warfarin use was comparable in the two groups. The mortality rate was 3-fold higher in the CAD group (33.8% vs. 13.1%, p=0.001).

11 Table 1: Overall analysis of DVT cases with Coronary artery Disease (n=65) Variables N (%) Variables N (%) Males 42 (64.6%) Hospital stay (days) 8 (2-270) Age (mean±sd) 63.9±15.9 Post-thrombotic syndrome 30 (46.2%) <40 years 6 (9.2%) Pulmonary Embolism 9 (13.8%) >40-59 years 20 (30.8%) Mortality 22 (33.8%) years 21 (32.3%) 75 years 18 (27.7%) Qatari 29 (44.6%) Body mass index 30.9±8.5

12 Table 2: Risk factors in DVT cases with Coronary artery Disease Variables N (%) Abnormal coagulation 11 (16.9%) Recurrent DVT 11 (16.9%) Malignancy 10 (15.4%) Paraplegia 2 (3.1%) Polytrauma 2 (3.1%) Obesity 30 (48.4%) Diabetes Mellitus 45 (69.2%) Hypertension 60 (92.3%) Hypercholesterolemia 54 (83.1%) Congestive heart failure 10 (15.4%)

13 Table 3: Site of thrombosis based on Doppler ultrasonography findings in CAD patients Variables N (%) Left lower limb 30 (50.8%) Right lower limb 28 (47.5%) Both lower limbs 1 (1.7%) Popliteal Vein 42 (64.6%) Posterior Tibial Vein 43 (66.2%) Profunda Femoris Vein 45 (69.2%) Common Femoral Vein 31 (47.7%) Great Saphenous Vein 9 (13.8%) Iliac vein 2 (3.1%)

14 Table 4: Laboratory findings of DVT cases with CAD Coagulation profiles Protein C deficiency 3 (4.6%) Protein S deficiency 3 (4.6%) Hyperhomocysteine 4 (6.2%) Antithrombin III deficiency 3 (4.6%) Factor V Leiden 2 (3.1%) Positive D Dimer (>0.55 mg/l) 46 (95.8%) Ejection Fraction (%) 46.1±12.4

15 Table 5: Comparison of demographics and risk factors (CAD vs. no-cad) Variables No-CAD CAD p-value Females Males Age (mean±sd) 48.7± ± <40 years >40-59 years years years Qatari

16 Table 5: Comparison of demographics and risk factors (CAD vs. no-cad) Variables No-CAD CAD p-value Risk factors Abnormal coagulation Recurrent DVT Malignancy History of Pulmonary Embolism History of surgery History of travel Paraplegia Bedridden Obesity Diabetes Mellitus Hypertension hypercholesterolemia Congestive heart failure

17 Table 6: Comparison of laboratory findings, treatment and outcome (CAD vs. no-cad) Variables No-CAD CAD p-value Thrombophilic disorders Protein C deficiency Protein S deficiency Hyperhomocysteine Anti thrombin III deficiency Factor V Leiden Treatment Warfarin Enoxaparin Aspirin Clopidogril Dalteparin Heparin Hospital stay (days) 7 (1-130) 8 (2-270) 0.18 Pulmonary Embolism 12.1 (n=72) 13.8 (n=9) 0.68 Mortality 13.1 (n=78) 33.8 (n=22) 0.001

18 56.3% CAD in DVT patients 20.3% 15.6% 7.8% NSETMI Unstable angina Stable angina STEMI

19 CAD & DVT Coronary angiography N=27 PCI (stenting) N=15 S/PCABG N=2 Microvascular/spasm? N=1 Ectatic vessels N=1 CAD for medical treatment N=10

20 Discussion Pathophysiological and epidemiological findings have enabled the definition of the main risk factors for atherothrombosis and VTE. The incidence rate of arterial thrombotic events after a first venous thrombosis was found as high as 2 to 5% per year. Limitations : the exact starting time of each process is not so clear in most of studies (egg & chicken?)

21 Possible explanation One explanation is the temporary inflammatory or pro-coagulant response due to sudden tissue damage or necrosis after the arterial thrombotic event onset. The arterial event leads to a certain situation (immobilization, necrosis) which in its turn increases the risk of venous thrombosis. Second, there is a possibility that the presence of atherosclerosis is a common cause of both arterial and venous thrombosis.

22 Third, risk factors that are associated with both venous and arterial thrombosis, such as obesity could explain the association. Atherosclerosis enhances inflammation and coagulation, Arterial and venous thrombosis are associated diseases through atherosclerosis treatment with vitamin K antagonists (for DVT) may lead to increased arterial calcification>>arterial thromb. However, all relationships between atherosclerosis, arterial and venous thrombosis could be explained by the presence of common risk factors. Semin Thromb Hemost Nov;37(8): doi: /s

23 Association between CVRF and CVD & VTE CVD OR (99% confidence interval) VTE OR (95% confidence interval) Dyslipidemia 3.25( ) - Smoking 2.87( ) 1.42( ) DM 2.37( ) 1.42( ) Hypertension 1.91( ) 1.51( ) Obesity 1.62( ) 2.33( ) some data showed 40-50% risk reduction for first VTE when using statins Previtali et al. Blood Transfus Apr;9(2): doi: / Semin Thromb Hemost Nov;37(8): doi: /s

24 Authors Country Study design Number of CAD Patients Number of DVT patients Median Follow Up (Years) Risk Factor Lind et al (2014) Norway Cohort Study Family History Environmental and Psychosocial factors Described mechanism and Pathophysiology Several genetic studies described the association between heart disease and VTE. Also, Inherited thrombophilic abnormalities i.e. Factor V Leiden and Prothrombin G20210A are associated with CAD. Conclusion Patient with family history of MI are at higher risk to develop MI and VTE. Mainly unprovoked Lind C, Flinterman L et al. (2014) Norway Cohort Study Age, gender, BMI, DM, HTN, Hypercholesterolemia, smoking, physical activity and Education, Hormone Replacement therapy 1. Genetic thrombophilia with high level of coagulation factors VIII, IX and XI, Plasminogen activator inhibitor- 1 and Von Willebrand Factor. 2. Vascular Calcification 3. Inflammation Women and younger men with VTE have higher risk of arterial thrombotic disease. However, only 1% of Arterial thrombotic event can be attributed to VTE. Gylnn & Rosner (2005) United States Prospective Study Age, BMI, DM, HTN, Hypercholesterolemia, smoking, physical activity, Education and alcohol consumption - Arterial and Venous thrombosis has different etiologies.

25 Conclusion Although, DVT and CAD have difference pathophysiology, there are certain risk factors that should be looked in for both. The mortality is triple in DVT patients when CAD is coexistence. Recognition of the common risk factors, if proven to be relevant for VTE, may substantially lower thromboembolic events and direct for a more efficent VTE preventive measures Further prospective studies are required to support our findings.

26 Thanks