Is there an association between atherosclerosis and chronic venous disease?

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Is there an association between atherosclerosis and chronic venous disease? Karel Roztocil, IKEM, Praha Hungarian Society of Angiology and Vascular Surgery Congress, Szombathely 2017

Disclosure Nothing to declare with regard to this communication 2

Independency of arterial and venous diseases Venous and arterial disorders are viewed as separate pathophysiological entities Separate arterial and venous medical branches, scientific societies, journals and conferences Angiology all vessels Phlebology - dealing with venous diseases

Possible links between arteries and veins An increasing body of evidence suggests the likelihood of a link between arterial and venous diseases 1981 perhaps first description of potential association in patients with varicose veins appeared population-based study (Ducemitiere et al.) after 6,5 years follow-up of patients with varicose veins higher risk for intermittent claudication / coronary heart disease

Framingham study Men and women with varicose veins had a higher incidence of atherosclerotic cardiovascular disease than those without varicose veins Statistically significant risk of coronary heart disease in women Am J Prev Med 1988, 4(2), 96-101 5

Tampere, Finland 2008 population-based study by Makivaara et al. 6874 patients, 5 years follow-up Angina pectoris, myocardial infarction, PAD, cerebrovascular disease were recorded in patients with varicose veins Incidence of PAD OR 3,1 6

Prague Pre- and Post-Menopausal Female Study Random sample of 902 women from the general population of district Prague 4 606 women (67,2%) reported symptoms of CVI cramps, aching, edema, etc. Examined for cardiovascular risk factors, ABI, carotid IMT Differences between women with and without symptoms Significantly higher prevalence of ABI of less than 0,9 observed in women with any of CVD symptoms Int. Angiol. 2011, 30, 335-41

Frequency of PAD in CVI 2014 - cross-sectional study at Vojvodina, Serbia Groups: 1) CVD CEAP 1-4 2) CVD CEAP 5-6 3) controls decrease of ABI in 20% of CVD in 10% of controls 8

Arterial and venous disease links Common risk factors age, obesity, diabetes, smoking, dyslipidemia etc. Common mechanisms for arterial and venous thrombosis hyperhomocysteinemia, factor V Leiden, prothrombin gene mutation, antiphospholipid antibodies

Venous thromboembolism and atherosclerosis Several studies have shown that patients with unprovoked VTE are at a higher risk of cardiovascular diseases, including atherosclerotic complications, than in the general population

VTE and risk of subsequent symptomatic atherosclerosis Prandoni et al. J.Thromb. Haemost. 2006 1919 consecutive patients with a 1. episode of VTE 4 years follow-up Incidence of fatal and nonfatal CV events Idiopathic VTE 15,1% Secondary VTE 8,5%

Cardiovascular events in patients with previous VTE

Is VTE predictive of arterial cardiovascular event? Retrospective study, mean follow-up 43 months Incidency of CV events 151 patients with unprovoked VTE 16 151 controls 6 Bova et al. Thromb Haemost 2006, 96, 132-6

Arterial events after unprovoked VTE and in controls

Common effect of drugs on arterial and venous diseases Examples from placebo controlled clinical trials confirming simultaneous effects of drugs on arterial and venous level prevention of arterial and venous TE: aspirin (WARFASA, ASPIRE) statins (JUPITER) Sulodexide (SURVET)

Effect of aspirin in ASPIRE and WARFASA studies Aspirin 100 mg/d reduced 32% of VTE episodes (P=0.007) and simultaneously 34% of cardiovascular events (m.i., strokes) without increased risk of bleeding = Prophylaxis of both arterial and venous thrombosis

Studie JUPITER Justification for the use of statin in prevention: an interventional trial evaluating rosuvastatin Reduced cardiovascular events together with reduced thromboembolic complications NEJM 2009, 360, 1851-61

SURVET Study Sulodexide administration reduced 50% of venous thrombosis recurences Indicated: 1. in patients with PAD for treatment of claudication 2. in patients with venous ulcers medikam. podpora lokální léčby 3. in secondary prevention of venous thromboembolism

Aim of our study: Detection of peripheral arterial occlusion disease in patients with chronic venous disease Comparison with controls Measurement of ABI for detection of PAD

Measurement of ankle-brachial index Non-invasive method used most frequently in clinical practice for detection and evaluation of PAD

Main advantages of ABI 1. relatively simple, non-expensive test 2. not time-consuming investigation 3. immediately obtained results 4. non-invasive and free of pain 5. may be repeted as often as necessary 6. not associated with any risk for patients

Main advantages of ABI (contin.) 7. hemodynamic parameter 8. additional information to imaging methods 9. availabiliy of instruments 10. pocket-size instruments for bed-side investigation 11. may be rutinely used in ambulatory setting 12. cardiovascular risk and prognosis evaluation

Main advatages of ABI (contin.) 13. high sensitivity and specificity 14. based on well-known principle of blood pressure measurement 15. quantitave parameter, understandable for other doctors 16. ability of early detection of asymptomatic patients 17. degree of functional deterioration 18. follow-up of therapeutic effects

Suitable methods for early detection of atherosclerosis Ankle-brachial index Intima-media thickness Endothelial function Coronary calcium score MRI AHA Prevention Conf. Circulation 2000, 101, 111-6

How to measure ABI correctly Guidelines for standardization of method: Measurement and interpretation of the ABI A Scientific statement from the American Heart Association Aboyans V. et al. Circulation 2012, 126, 2890-2909

Guidelines for measurement of systolic blood pressures on 4 extremities (AHA 2012) 1. Doppler + cuffs 2. process: first arm first ankle (ATP, ADP) second ankle (ATP, ADP) second arm 3. if systolic BP on any arm is different more than 10mmHg - repeat measurement

Manual measurement of ABI with Doppler May be more challenging in patients with PAD in whom pulses are missing and difficult to detect by Doppler May require a degree of expertise May require an amount of time to be performed More simple approach: automated oscillometric devices

Automated oscillometric ABI measurement ABI determination more simple, easy to perform Simultaneous assessment of all four extremities, avoiding a potential bias by variations of blood pressure Reduction of examination time

Recommendations for use and interpretation of the ABI in PAD (AHA 2012) ABI in rest may be in normal range if the stenosis is not significant In this case postexercise ABI should be measured to detect it and improve sensitivity of the test

Measurement of postexercise ABI by automated oscillometry to increase sensitivity of automated investigation After standard measurement in rest a patient was asked to exercise for 1 min with elevated lower limbs - dorsal-plantar flexition in ankle (elevation/dependency test) Second measurement immediately after exercise

Material: CVI: 22 patients ( 47 85 years, 10 male, 12 female) 44 legs PAD: 36 patients ( 50 95 years, 26 male, 10 female) 72 legs Controls: 14 persons (45-78 years, 8 male, 7 female) 28 legs

Mean values of ABI in rest and after exercise resting after exercise Controls 1.06+-0.018 1.03+-0.018 CVD 1.09+-0.013 1.03+-0.012 PAD 0.87+-0.026 0.074+-0.040

Mean decrease of ABI after exercise Controls CVI PAD

ABI in patients with chronic venous disease Decrease of ABI after exercise in patients with CVD significantly higher than in controls without vascular disorders, but lower than in patients with PAD Presence of subclinical asymptomatic PAD Chronic arterial and venous diseases could be associated with similar processes at the endothelial level

Conclusion Good agreement of our findings with previous studies There is probably an association between VTE as well as CVD and atherosclerosis with increased risk of subsequent CV events Common risk factors and pathogenesis of chronic arterial and venous diseases suspected Implication: patients with history of VTE and CVD should be investigated for asymptomatic atherosclerosis and modification of risk profile in those with abnormal results

Thank you for your attention 38

Thank you for your attention