Cardiology 2015: Peripheral Circulation

    Authors

    Abstract

    ## Introduction At the initiative of the Croatian Cardiac Society (CCS), the Working Group on Angiology and Peripheral Vascular Diseases decided to address the state of Croatian angiology during 2015, based on the example of the Working Group on Peripheral Circulation of the European Society of Cardiology that was published in the European Heart Journal. The goal was to provide an overview of the positions and goals that CCS holds, based on the current knowledge and events in the European cardiologic community that marked the year 2015. (1) This editorial will briefly address the prevention of cardiovascular diseases and the importance of new markers in cardiovascular identification, diagnosis and treatment of peripheral artery disease, and finally the current issues related to venous thromboembolism treatment. ## Prevention of cardiovascular diseases Prevention of cardiovascular diseases is still very topical, and has in recent years increasingly included the expanded “vascular territories”, primarily carotid and peripheral circulation, in the assessment of cardiovascular risk. **Table 1** includes some of the recommendations published in current guidelines for the prevention of cardiovascular diseases (2) by the European Society of Cardiology (ESC) in May 2016. ### Table 1: Methods of cardiovascular risk assessment – using insight into the state of peripheral blood vessels (modified from reference 2 ). | **Recommendations** | **Class / Level** | | --- | --- | | Atherosclerotic plaque detection by carotid artery scanning may be considered as a risk modifier in cardiovascular risk assessment. | IIb / B | | Ankle-brachial index may be considered as a risk modifier in cardiovascular risk assessment. | IIb / B | | Carotid ultrasound intima-media thickness screening for cardiovascular risk assessment is not recommended. | III / A | Carotid intima-media thickness (CIMT) has become interesting clinical evidence and a marker in the focus of cardiovascular research as a potential challenge in the reclassification of cardiovascular risk, although current guidelines do not recommend it for routine application. A prospective multi-center study found that CIMT measurement was associated with cardiovascular events in participants under 45 years of age. (3) CIMT increase did not provide further information beyond that from the standard risk factors, but the study supported its use as a biomarker for persons that are still not qualified for screening for standard cardiovascular risk factors, given that these are usually used in persons above 40 years of age. (1) The position of CCS on this issue is fully in line with the ESC guidelines published in 2012 and 2016 (2, 4) (**Table 2**), although CIMT is still in the category of professional and scientific interest regarding cardiovascular risk assessment in our relatively small cardiovascular community and has no wider clinical application in routine risk assessment. CCS shares the positions and adheres to the rules of ESC, which states that CIMT measurement could cause inadequate concern and treatment in cases of false-positive results, but even a negative result could lead to unnecessary laxity and a false sense of safety regarding the proper relationship to a healthy lifestyle. Thus, the systematic assessment of cardiovascular risk in men younger than 40 years of age and women younger than 50 remains advocated by the newest guidelines on cardiovascular prevention published in 2016. ### Table 2: From the current cardiovascular disease prevention guidelines of the European Society of Cardiology (modified from reference 2 ). | **Recommendations** | **Class / Level** | | --- | --- | | Systematic cardiovascular risk assessment is recommended in individuals at increased cardiovascular risk, i.e. with family history of premature cardiovascular disease, familial hyperlipidaemia, major cardiovascular risk factors (such as smoking, high blood pressure, diabetes or raised lipid levels) or comorbidities increasing cardiovascular risk. | I / C | | It is recommended to repeat cardiovascular risk assessment every 5 years, and more often for individuals with risks close to thresholds mandating treatment. | I / C | | Systematic cardiovascular risk assessment may be considered in men >40 years of age and in women >50 years of age or post-menopausal with no known cardiovascular risk factors. | IIb / C | | Systematic cardiovascular risk assessment in men th CCS congress in October 2014. The results of the poll, in which 88 physicians took part (62 cardiologists, 14 internists, and 12 other physicians with other specialties) bear witness to the neglect for this method in the overall cardiologic practice. Approximately 20% of the participants responded to the poll. Active participation in the diagnostic process and assessment of peripheral artery disease did not include any method in the diagnosis of peripheral arterial disease for 56% of those polled, and only 7% used ABI as a screening method and as the initial, key method in the severity assessment in peripheral artery disease. A total of 55% respondents believed that ABI measurement would contribute to total cardiovascular status assessment in patients during routine assessment of arterial disease. All this indicates the need to once again ensure adherence to recommendations in the ESC guidelines for the diagnosis and treatment of peripheral artery disease that were presented as early as 2011 and were translated as summarized guidelines in the Republic of Croatia in 2013. (9, 10) We believe it would be worthwhile to alert the cardiologic public to the importance of the application of vascular biomarkers in primary and secondary cardiovascular prevention, so in **Table 4** we showed only the most important biomarkers with A-level evidence that have been accepted so far. ### Table 4: The applicability of vascular biomarkers in primary and secondary cardiovascular prevention (modified from reference 1 ). | Vascular biomarker | Class / Level | Risk stratification value / Simplicity of method | | --- | --- | --- | | **Ankle-brachial index** | IIa / A | +++ / ++++ | | Arterial stiffness | | | | Pulse wave velocity (carotid, femoral artery) | IIa / A | ++++ / +++ | | Carotid ultrasound | IIa / A | +++ / ++ | ## Peripheral artery disease The diagnostic process and disease assessment for peripheral artery diseases, despite the published guidelines, still relies only on clinical signs, arterial circulation duplex ultrasound, and angiography. Only a negligible number of centers use plethysmography, segmental blood pressure, and ABI in the diagnostic process, despite the fact that this method is an indispensable part of peripheral artery disease assessment. Based on data from the Information Health System of the Republic of Croatia (CEZIH) of the Croatian Health Insurance Fund (HZZO), a total of 644 angiointerventions on peripheral arteries were performed in 2015 in the Republic of Croatia (527 with the implantation of 1 stent and 117 with the implantation of 2 or more stents). This number also includes carotid artery interventions. Carotid endarterectomy, based on the same data, was performed in 1213 carotid arteries, which is in line with the recommendations and evidence from the publication we are referring to, suggesting that endarterectomy is a method that is still preferred over endovascular treatment for carotid stenosis. ## Vein thrombosis Public awareness is low regarding venous thromboembolism (VTE) and deep vein thrombosis (DVT) as well as pulmonary embolism (PE) and is estimated at 44% to 59%, which is lower than awareness of myocardial infarction (88%) and stroke (90%) as well as arterial hypertension (90%). (11) Additional public or media engagement is necessary in order to increase public awareness of the significance of VTE and thus reduce the disease burden of this widespread but preventable disease. We do not have clear objective data on the prevalence of venous thrombosis for the Republic of Croatia, since a registry for venous thrombosis does not exist. Knowing the true prevalence of the disease is only partially possible, since data only applies to the hospitalized part of the population. According to data from the CEZIH/HZZO database for 2015, it is estimated that approximately 1925 patients were treated for venous thrombosis in hospital conditions. It is not possible to determine the data on the true incidence of the disease based on this number of patients that had venous thrombosis as their initial diagnosis. If we accept that the incidence of venous thrombosis in Croatia is similar to the incidence reported in European and US publications, we can expect that the annual incidence in the general population is between 6000 and 7000 cases. It is important to once again point out the abovementioned results of the poll on the way VTE is being treated. The data show that 68% of physicians believe that the application of vitamin K antagonists (VKA) in the treatment of DVT and thromboembolism prophylaxis is a cause for concern, since only 30% that patients treated with VKA achieve target international normalized ratios (INR). Approximately 88% hold that the application of new oral anticoagulants would contribute to better compliance, comfort, and safety for venous thrombosis treatment. Approximately 70% of the respondents believed this would also reduce treatment costs for patients with DVT due to the increase in effectiveness, especially due to lower incidence of side effects. The initiative of the Working Group on Angiology and Peripheral Vascular Diseases of the CCS to improve interest and awareness of venous thrombosis is related to the preparation of the National Guidelines for the Diagnosis and Treatment of Venous Thrombosis and Venous Thromboembolism, which will soon be presented to the public and which, given the lack of ESC guidelines on the diagnosis and treatment of venous thrombosis, mostly rely on the recommendations published in the Chest Journal during 2016 and treatment guidelines for acute pulmonary embolism. (12, 13) ## Conclusion We believe it is not irrelevant that as many as 78% of cardiologists thought that further education in angiology should be ensured for the treatment and diagnostics of venous diseases and peripheral artery diseases. To satisfy these needs, which would lead to better clinical practice and compliance with current guidelines, it is necessary to achieve synergy between the possibilities determined by the Croatian Health Insurance Fund, but also strengthen the initiative of the CCS, encourage and develop registries in the field of angiology, and encourage professionals to be sensitive to the issues related to angiology in the Republic of Croatia. We also believe it is important to emphasize that in addition to the CCS, the scientific and professional activities of the Croatian Academy of Sciences and Arts in 2015 also contributed to public and professional awareness of the academic community regarding the current topics in peripheral artery diseases and biomarkers in cardiovascular risk assessment.

    DOI

    https://doi.org/10.15836/ccar2016.314

    Literature

    1. Aboyans V, De Carlo M, Kownator S, Mazzolai L, Meneveau N, Ricco JB, et al. The year in cardiology 2015: peripheral circulation. Eur Heart J. 2016;37(8):676–85. https://doi.org/10.1093/eurheartj/ehv709
    2. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 May 23;•••:ehw106.; Epub ahead of print. https://doi.org/10.1093/eurheartj/ehw106
    3. Eikendal AL, Groenewegen KA, Anderson TJ, Britton AR, Engström G, Evans GW, et al. Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years. Hypertension. 2015;65(4):707–13. https://doi.org/10.1161/HYPERTENSIONAHA.114.04658
    4. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701. https://doi.org/10.1093/eurheartj/ehs092
    5. Vrkić Kirhmajer M. Debljina intima medija arterija u procjeni asimptomatske ateroskleroze. In: Zbornik radova sa znanstvenog skupa HAZU "Prevencija ateroskleroze". 2015 Apr 9; Zagreb, Croatia. Zagreb: Hrvatska akademija znanosti i umjetnosti; 2015. p. 49-59.
    6. Banfić Lj. Personalizirana prevencija asimptomatske ateroskleroze. In: Zbornik radova sa znanstvenog skupa HAZU "Prevencija ateroskleroze". 2015 Apr 9; Zagreb, Croatia. Zagreb: Hrvatska akademija znanosti i umjetnosti; 2015. p. 1-10.
    7. Banfić L, Miovski Z. P3628: Pulse wave velocity (PWV), augmentation index (AIx) or beta index as the surrogate marker for coronary disease or arterial ageing only. Eur Heart J. 2014;35 suppl 1:661.
    8. Townsend N, Nichols M, Scarborough P, Rayner M. Cardiovascular disease in Europe-epidemiological update 2015. Eur Heart J. 2015;36(40):2696–705. https://doi.org/10.1093/eurheartj/ehv428
    9. European Stroke Organisation, Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clément D, Collet JP, et al. ESC Committee for Practice Guidelines. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(22):2851–906. https://doi.org/10.1093/eurheartj/ehr211
    10. Sažete smjernice Europskog kardiološkog društva za dijagnostiku i liječenje periferne arterijske bolesti (hrvatsko izdanje). Zagreb: Hrvatsko kardiološko društvo; 2013.
    11. Wendelboe AM, McCumber M, Hylek EM, Buller H, Weitz JI, Raskob G, ISTH Steering Committee for World Thrombosis Day. Global public awareness of venous thromboembolism. J Thromb Haemost. 2015;13(8):1365–71. https://doi.org/10.1111/jth.13031
    12. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315–52. https://doi.org/10.1016/j.chest.2015.11.026
    13. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galič N, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033–69, 3069a–3069k. https://doi.org/10.1093/eurheartj/ehu283
    Cardiologia Croatica
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    Cardiology 2015: Peripheral Circulation

    Editorial
    Issue8
    Published
    Pages314-318
    PDF via DOIhttps://doi.org/10.15836/ccar2016.314

    Authors

    Ljiljana Banfić*ORCIDWorking Group on Angiology and Peripheral Vascular Diseases, Croatian Cardiac Society, Croatia

    *Correspondence email: ljiljanabanfic@yahoo.com

    Abstract

    ## Introduction At the initiative of the Croatian Cardiac Society (CCS), the Working Group on Angiology and Peripheral Vascular Diseases decided to address the state of Croatian angiology during 2015, based on the example of the Working Group on Peripheral Circulation of the European Society of Cardiology that was published in the European Heart Journal. The goal was to provide an overview of the positions and goals that CCS holds, based on the current knowledge and events in the European cardiologic community that marked the year 2015. (1) This editorial will briefly address the prevention of cardiovascular diseases and the importance of new markers in cardiovascular identification, diagnosis and treatment of peripheral artery disease, and finally the current issues related to venous thromboembolism treatment. ## Prevention of cardiovascular diseases Prevention of cardiovascular diseases is still very topical, and has in recent years increasingly included the expanded “vascular territories”, primarily carotid and peripheral circulation, in the assessment of cardiovascular risk. **Table 1** includes some of the recommendations published in current guidelines for the prevention of cardiovascular diseases (2) by the European Society of Cardiology (ESC) in May 2016. ### Table 1: Methods of cardiovascular risk assessment – using insight into the state of peripheral blood vessels (modified from reference 2 ). | **Recommendations** | **Class / Level** | | --- | --- | | Atherosclerotic plaque detection by carotid artery scanning may be considered as a risk modifier in cardiovascular risk assessment. | IIb / B | | Ankle-brachial index may be considered as a risk modifier in cardiovascular risk assessment. | IIb / B | | Carotid ultrasound intima-media thickness screening for cardiovascular risk assessment is not recommended. | III / A | Carotid intima-media thickness (CIMT) has become interesting clinical evidence and a marker in the focus of cardiovascular research as a potential challenge in the reclassification of cardiovascular risk, although current guidelines do not recommend it for routine application. A prospective multi-center study found that CIMT measurement was associated with cardiovascular events in participants under 45 years of age. (3) CIMT increase did not provide further information beyond that from the standard risk factors, but the study supported its use as a biomarker for persons that are still not qualified for screening for standard cardiovascular risk factors, given that these are usually used in persons above 40 years of age. (1) The position of CCS on this issue is fully in line with the ESC guidelines published in 2012 and 2016 (2, 4) (**Table 2**), although CIMT is still in the category of professional and scientific interest regarding cardiovascular risk assessment in our relatively small cardiovascular community and has no wider clinical application in routine risk assessment. CCS shares the positions and adheres to the rules of ESC, which states that CIMT measurement could cause inadequate concern and treatment in cases of false-positive results, but even a negative result could lead to unnecessary laxity and a false sense of safety regarding the proper relationship to a healthy lifestyle. Thus, the systematic assessment of cardiovascular risk in men younger than 40 years of age and women younger than 50 remains advocated by the newest guidelines on cardiovascular prevention published in 2016. ### Table 2: From the current cardiovascular disease prevention guidelines of the European Society of Cardiology (modified from reference 2 ). | **Recommendations** | **Class / Level** | | --- | --- | | Systematic cardiovascular risk assessment is recommended in individuals at increased cardiovascular risk, i.e. with family history of premature cardiovascular disease, familial hyperlipidaemia, major cardiovascular risk factors (such as smoking, high blood pressure, diabetes or raised lipid levels) or comorbidities increasing cardiovascular risk. | I / C | | It is recommended to repeat cardiovascular risk assessment every 5 years, and more often for individuals with risks close to thresholds mandating treatment. | I / C | | Systematic cardiovascular risk assessment may be considered in men >40 years of age and in women >50 years of age or post-menopausal with no known cardiovascular risk factors. | IIb / C | | Systematic cardiovascular risk assessment in men th CCS congress in October 2014. The results of the poll, in which 88 physicians took part (62 cardiologists, 14 internists, and 12 other physicians with other specialties) bear witness to the neglect for this method in the overall cardiologic practice. Approximately 20% of the participants responded to the poll. Active participation in the diagnostic process and assessment of peripheral artery disease did not include any method in the diagnosis of peripheral arterial disease for 56% of those polled, and only 7% used ABI as a screening method and as the initial, key method in the severity assessment in peripheral artery disease. A total of 55% respondents believed that ABI measurement would contribute to total cardiovascular status assessment in patients during routine assessment of arterial disease. All this indicates the need to once again ensure adherence to recommendations in the ESC guidelines for the diagnosis and treatment of peripheral artery disease that were presented as early as 2011 and were translated as summarized guidelines in the Republic of Croatia in 2013. (9, 10) We believe it would be worthwhile to alert the cardiologic public to the importance of the application of vascular biomarkers in primary and secondary cardiovascular prevention, so in **Table 4** we showed only the most important biomarkers with A-level evidence that have been accepted so far. ### Table 4: The applicability of vascular biomarkers in primary and secondary cardiovascular prevention (modified from reference 1 ). | Vascular biomarker | Class / Level | Risk stratification value / Simplicity of method | | --- | --- | --- | | **Ankle-brachial index** | IIa / A | +++ / ++++ | | Arterial stiffness | | | | Pulse wave velocity (carotid, femoral artery) | IIa / A | ++++ / +++ | | Carotid ultrasound | IIa / A | +++ / ++ | ## Peripheral artery disease The diagnostic process and disease assessment for peripheral artery diseases, despite the published guidelines, still relies only on clinical signs, arterial circulation duplex ultrasound, and angiography. Only a negligible number of centers use plethysmography, segmental blood pressure, and ABI in the diagnostic process, despite the fact that this method is an indispensable part of peripheral artery disease assessment. Based on data from the Information Health System of the Republic of Croatia (CEZIH) of the Croatian Health Insurance Fund (HZZO), a total of 644 angiointerventions on peripheral arteries were performed in 2015 in the Republic of Croatia (527 with the implantation of 1 stent and 117 with the implantation of 2 or more stents). This number also includes carotid artery interventions. Carotid endarterectomy, based on the same data, was performed in 1213 carotid arteries, which is in line with the recommendations and evidence from the publication we are referring to, suggesting that endarterectomy is a method that is still preferred over endovascular treatment for carotid stenosis. ## Vein thrombosis Public awareness is low regarding venous thromboembolism (VTE) and deep vein thrombosis (DVT) as well as pulmonary embolism (PE) and is estimated at 44% to 59%, which is lower than awareness of myocardial infarction (88%) and stroke (90%) as well as arterial hypertension (90%). (11) Additional public or media engagement is necessary in order to increase public awareness of the significance of VTE and thus reduce the disease burden of this widespread but preventable disease. We do not have clear objective data on the prevalence of venous thrombosis for the Republic of Croatia, since a registry for venous thrombosis does not exist. Knowing the true prevalence of the disease is only partially possible, since data only applies to the hospitalized part of the population. According to data from the CEZIH/HZZO database for 2015, it is estimated that approximately 1925 patients were treated for venous thrombosis in hospital conditions. It is not possible to determine the data on the true incidence of the disease based on this number of patients that had venous thrombosis as their initial diagnosis. If we accept that the incidence of venous thrombosis in Croatia is similar to the incidence reported in European and US publications, we can expect that the annual incidence in the general population is between 6000 and 7000 cases. It is important to once again point out the abovementioned results of the poll on the way VTE is being treated. The data show that 68% of physicians believe that the application of vitamin K antagonists (VKA) in the treatment of DVT and thromboembolism prophylaxis is a cause for concern, since only 30% that patients treated with VKA achieve target international normalized ratios (INR). Approximately 88% hold that the application of new oral anticoagulants would contribute to better compliance, comfort, and safety for venous thrombosis treatment. Approximately 70% of the respondents believed this would also reduce treatment costs for patients with DVT due to the increase in effectiveness, especially due to lower incidence of side effects. The initiative of the Working Group on Angiology and Peripheral Vascular Diseases of the CCS to improve interest and awareness of venous thrombosis is related to the preparation of the National Guidelines for the Diagnosis and Treatment of Venous Thrombosis and Venous Thromboembolism, which will soon be presented to the public and which, given the lack of ESC guidelines on the diagnosis and treatment of venous thrombosis, mostly rely on the recommendations published in the Chest Journal during 2016 and treatment guidelines for acute pulmonary embolism. (12, 13) ## Conclusion We believe it is not irrelevant that as many as 78% of cardiologists thought that further education in angiology should be ensured for the treatment and diagnostics of venous diseases and peripheral artery diseases. To satisfy these needs, which would lead to better clinical practice and compliance with current guidelines, it is necessary to achieve synergy between the possibilities determined by the Croatian Health Insurance Fund, but also strengthen the initiative of the CCS, encourage and develop registries in the field of angiology, and encourage professionals to be sensitive to the issues related to angiology in the Republic of Croatia. We also believe it is important to emphasize that in addition to the CCS, the scientific and professional activities of the Croatian Academy of Sciences and Arts in 2015 also contributed to public and professional awareness of the academic community regarding the current topics in peripheral artery diseases and biomarkers in cardiovascular risk assessment.

    Literature

    1. 1.
      Aboyans V, De Carlo M, Kownator S, Mazzolai L, Meneveau N, Ricco JB, et al. The year in cardiology 2015: peripheral circulation. Eur Heart J. 2016;37(8):676–85.DOI
    2. 2.
      Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 May 23;•••:ehw106.; Epub ahead of print.DOI
    3. 3.
      Eikendal AL, Groenewegen KA, Anderson TJ, Britton AR, Engström G, Evans GW, et al. Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years. Hypertension. 2015;65(4):707–13.DOI
    4. 4.
      Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701.DOI
    5. 5.
      Vrkić Kirhmajer M. Debljina intima medija arterija u procjeni asimptomatske ateroskleroze. In: Zbornik radova sa znanstvenog skupa HAZU "Prevencija ateroskleroze". 2015 Apr 9; Zagreb, Croatia. Zagreb: Hrvatska akademija znanosti i umjetnosti; 2015. p. 49-59.
    6. 6.
      Banfić Lj. Personalizirana prevencija asimptomatske ateroskleroze. In: Zbornik radova sa znanstvenog skupa HAZU "Prevencija ateroskleroze". 2015 Apr 9; Zagreb, Croatia. Zagreb: Hrvatska akademija znanosti i umjetnosti; 2015. p. 1-10.
    7. 7.
      Banfić L, Miovski Z. P3628: Pulse wave velocity (PWV), augmentation index (AIx) or beta index as the surrogate marker for coronary disease or arterial ageing only. Eur Heart J. 2014;35 suppl 1:661.
    8. 8.
      Townsend N, Nichols M, Scarborough P, Rayner M. Cardiovascular disease in Europe-epidemiological update 2015. Eur Heart J. 2015;36(40):2696–705.DOI
    9. 9.
      European Stroke Organisation, Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clément D, Collet JP, et al. ESC Committee for Practice Guidelines. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(22):2851–906.DOI
    10. 10.
      Sažete smjernice Europskog kardiološkog društva za dijagnostiku i liječenje periferne arterijske bolesti (hrvatsko izdanje). Zagreb: Hrvatsko kardiološko društvo; 2013.
    11. 11.
      Wendelboe AM, McCumber M, Hylek EM, Buller H, Weitz JI, Raskob G, ISTH Steering Committee for World Thrombosis Day. Global public awareness of venous thromboembolism. J Thromb Haemost. 2015;13(8):1365–71.DOI
    12. 12.
      Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315–52.DOI
    13. 13.
      Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galič N, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033–69, 3069a–3069k.DOI