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Коагулогические факторы риска сердечно-сосудистых заболеваний в популяции взрослого населения Томска
Коагулогические факторы риска сердечно-сосудистых заболеваний в популяции взрослого населения Томска
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Аннотация
В работе представлен анализ уровня фибриногена, D-димера и глобального показателя, характеризующего антикоагулянтную функцию системы протеина С (ТромбоПас), у 1104 обследованных из взрослого неорганизованного населения 25–64 лет г. Томска, выполненный в рамках проекта ЭССЕ РФ – 2012 (Эпидемиология Сердечно-Сосудистых заболеваний в рЕгионах Российской Федерации). Проанализированы взаимосвязи этих показателей с основными демографическими и клиническими характеристиками. Наличие хотя бы одного из маркеров гиперкоагуляции, к которым относили уровень фибриногена, превышающий 3,7 г/л, D-димера – 500 нг/мл, а индекс ингибирования образования тромбина в тесте ТромбоПас (PICI%) ниже или равный 84%, выявлено у 55,44% обследованных. При этом у 2,72% обследованной популяции наблюдалось сочетание всех трех маркеров гиперкоагуляции, сочетание как минимум одного из маркеров гиперкоагуляции и/или таких факторов риска, как артериальная гипертония (АГ) и ожирение (индекс массы тела – 30 кг/м2 и более), наблюдалось у 36,87% обследованных. Маркеры гиперкоагуляции, АГ и ожирение отсутствовали лишь у 19,47% обследованных. Таким образом, результаты исследования свидетельствуют о высоком риске тромботических осложнений сердечно-сосудистых заболеваний в исследованной группе населения и обосновывают целесообразность разработки адекватных методов их профилактики.
Ключевые слова: эпидемиологическое исследование, взрослое население, фибриноген, D-димер, система протеина С, ожирение, артериальная гипертония.
The relationships of these parameters with the main demographic and clinical characteristics were analyzed. The presence of at least one of the markers of hypercoagulability, which include fibrinogen level higher than 3,7 g/l D-dimer – 500 ng / ml, and the index of inhibition of thrombin formation in the TromboPas (PICI%) test, that islower or equal to 84%, was found in 55,44% of the patients. At the same time, in 2,72% of the surveyed population a combination of all three hypercoagulation markers was observed, whereas a combination of at least one of the mentioned markers and / or risk factors such as arterial hypertension (AH) and obesity (BMI≥30 kg/m2) was observed in 36,87% of patients. Hypercoagulation markers, hypertension and obesity were absent only in 19,47% of patients. Thus, the results suggest a high risk of thrombotic complications of cardiovascular disease (CVD) in the studied population and justify the feasibility of developing adequate methods to prevent them.
Key words: an epidemiological study, the adult population, fibrinogen, D-dimer, protein C system, obesity, hypertension.
Ключевые слова: эпидемиологическое исследование, взрослое население, фибриноген, D-димер, система протеина С, ожирение, артериальная гипертония.
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The relationships of these parameters with the main demographic and clinical characteristics were analyzed. The presence of at least one of the markers of hypercoagulability, which include fibrinogen level higher than 3,7 g/l D-dimer – 500 ng / ml, and the index of inhibition of thrombin formation in the TromboPas (PICI%) test, that islower or equal to 84%, was found in 55,44% of the patients. At the same time, in 2,72% of the surveyed population a combination of all three hypercoagulation markers was observed, whereas a combination of at least one of the mentioned markers and / or risk factors such as arterial hypertension (AH) and obesity (BMI≥30 kg/m2) was observed in 36,87% of patients. Hypercoagulation markers, hypertension and obesity were absent only in 19,47% of patients. Thus, the results suggest a high risk of thrombotic complications of cardiovascular disease (CVD) in the studied population and justify the feasibility of developing adequate methods to prevent them.
Key words: an epidemiological study, the adult population, fibrinogen, D-dimer, protein C system, obesity, hypertension.
Полный текст
Список литературы
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8. Ye Z, Liu EH, Higgins JP et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367: 651–8.
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10. Lemkes BA, Hermanides J, DeVries JH et al. Hyperglycemia: a prothrombotic factor? J Thromb Haemost 2010; 8: 1663–9.
11. Meade TW, North WR, Chakrabarti R et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; 1 (8177): 1050–4.
12. Di Castelnuovo A, de Curtis A, Costanzo S et al on behalf of the MOLI-SANI Project Investigators. Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study. Haematologica 2013; 98 (9): 1476–80.
13. Willeit P, Thompson A, Aspelund T et al. Hemostatic Factors and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Updated Meta-Analyses. PLoS ONE 2013; 8 (2): e55175. doi:10.1371/journal.pone.0055175
14. Toulon P, Smirnov M, Triscott M et al. A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway. Results of a multicenter study. Thromb Res 2009; 124: 137–43.
15. Ferroni P, Della-Morte D, Pileggi A et al. Impact of Statins on the Coagulation Status of Type 2 Diabetes Patients Evaluated by a Novel Thrombin-Generation Assay. Cardiovasc Drugs Ther 2012; 26: 301–9.
16. Ferroni P, Riondino S, Portarena I et al. Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer. Int J Colorectal Dis 2012: DOI 10.1007/s00384-012-1493-8
17. Чазова И.Е., Трубачева И.А., Жернакова Ю.В. и др. Распространенность артериальной гипертонии как фактора риска сердечно-сосудистых заболеваний в крупном городе сибирского федерального округа. Этот выпуск.
18. Koenig W. Fibrin (ogen) in cardiovascular disease: an update. Thromb Haemost 2003; 89: 601–9.
19. Stone MC, Thorp JM. Plasma fibrinogen – a major coronary risk factor. J R Coll Gen Pract 1985; 35 (281): 565–9.
20. Assmann G, Cullen P, Schulte H. The Münster Heart Study (PROCAM). Results of follow-up at 8 years. Eur Heart J 1998; 19 (Suppl. A): A2-11.
21. Thompson SG, Kienast J, Pyke SD et al. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332 (10): 635–41.
22. Kaptoge S, Di Angelantonio E, Pennells L. The Emerging Risk Factors Collaboration. C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction. N Engl J Med 2012; 367 (14): 1310–20.
23. Rudnicka AR, Rumley A, Lowe GDO, Strachan DP. Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population. Circulation 2007; 115: 996–1003.
24. Pandey AK, Pandey S, Blaha M et al. Family history of coronary heart disease and markers of subclinical cardiovascular disease: Wh ere do we stand? Atherosclerosis 2013; 228: 285e294.
25. Komarov AL, Panchenko EP, Dobrovolsky AB et al. D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease. Eur Heart J 2002; 23: 1309–16.
26. Воробьева Н.М., Панченко Е.П., Добровольский А.Б. и др. Повышение Д-димера у больных сердечно-сосудистыми заболеваниями без тромбоэмболических осложнений: с чем это связано и что делать? Ангиология и сосудистая хирургия. 2010; 16 (4): 34–42.
27. Di Nisio M, Squizzato A, Rutjes AWS et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 5: 296–304.
28. Lowe GDO, Rumley A, Sweetnam PM et al. Fibrin D-dimer, Markers of Coagulation Activation and the Risk of Major Ischaemic Heart Disease in the Caerphilly Study. Thromb Haemost 2001; 85: 822–7.
29. Woodward M, Rumley A, Welsh P et al. A comparison of the associations between seven hemostatic or inflammatory variables and coronary heart disease. J Thromb Haemost 2007; 5: 1795–800.
2. Трубачева И.А., Перминова О.А., Шатров С.В. и др. Изучение особенностей распределения уровней артериального давления и распространенности артериальной гипертонии у взрослого населения г. Томска. Кардиология. 2003; 11: 27–31.
3. Kenet G, Lutkhoff LK et al. Impact of Thrombophilia on Risk of Arterial Ischemic Stroke or Cerebral Sinovenous Thrombosis in Neonates and Children A Systematic Review and Meta-Analysis of Observational Studies. Circulation 2010; 121: 1838–47.
4. Mahmoodi BK, Brouwer J-LP, Veeger NJGM, van der Meer J. Hereditary Deficiency of Protein C or Protein S Confers Increased Risk of Arterial Thromboembolic Events at a Young Age. Results Fr om a Large Family Cohort Study. Circulation 2008; 118: 1659–67.
5. Lijfering WM, Brouwer J-LP, Veeger NJGM et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 2009; 113: 5314–22.
6. Gohil R, Peck G, Sharma P. The genetics of venous thromboembolism. A meta-analysis involving ~120,000 cases and 180,000 controls. Thromb Haemost 2009; 102: 360–70.
7. Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 2003; 146 (6): 948–57.
8. Ye Z, Liu EH, Higgins JP et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367: 651–8.
9. Viles-Gonzalez JF, Fuster V, Badimon JJ. Atherothrombosis: A widespread disease with unpredictable and life-threatening consequences. Eur Heart J 2004; 25: 1197–207.
10. Lemkes BA, Hermanides J, DeVries JH et al. Hyperglycemia: a prothrombotic factor? J Thromb Haemost 2010; 8: 1663–9.
11. Meade TW, North WR, Chakrabarti R et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; 1 (8177): 1050–4.
12. Di Castelnuovo A, de Curtis A, Costanzo S et al on behalf of the MOLI-SANI Project Investigators. Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study. Haematologica 2013; 98 (9): 1476–80.
13. Willeit P, Thompson A, Aspelund T et al. Hemostatic Factors and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Updated Meta-Analyses. PLoS ONE 2013; 8 (2): e55175. doi:10.1371/journal.pone.0055175
14. Toulon P, Smirnov M, Triscott M et al. A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway. Results of a multicenter study. Thromb Res 2009; 124: 137–43.
15. Ferroni P, Della-Morte D, Pileggi A et al. Impact of Statins on the Coagulation Status of Type 2 Diabetes Patients Evaluated by a Novel Thrombin-Generation Assay. Cardiovasc Drugs Ther 2012; 26: 301–9.
16. Ferroni P, Riondino S, Portarena I et al. Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer. Int J Colorectal Dis 2012: DOI 10.1007/s00384-012-1493-8
17. Чазова И.Е., Трубачева И.А., Жернакова Ю.В. и др. Распространенность артериальной гипертонии как фактора риска сердечно-сосудистых заболеваний в крупном городе сибирского федерального округа. Этот выпуск.
18. Koenig W. Fibrin (ogen) in cardiovascular disease: an update. Thromb Haemost 2003; 89: 601–9.
19. Stone MC, Thorp JM. Plasma fibrinogen – a major coronary risk factor. J R Coll Gen Pract 1985; 35 (281): 565–9.
20. Assmann G, Cullen P, Schulte H. The Münster Heart Study (PROCAM). Results of follow-up at 8 years. Eur Heart J 1998; 19 (Suppl. A): A2-11.
21. Thompson SG, Kienast J, Pyke SD et al. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332 (10): 635–41.
22. Kaptoge S, Di Angelantonio E, Pennells L. The Emerging Risk Factors Collaboration. C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction. N Engl J Med 2012; 367 (14): 1310–20.
23. Rudnicka AR, Rumley A, Lowe GDO, Strachan DP. Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population. Circulation 2007; 115: 996–1003.
24. Pandey AK, Pandey S, Blaha M et al. Family history of coronary heart disease and markers of subclinical cardiovascular disease: Wh ere do we stand? Atherosclerosis 2013; 228: 285e294.
25. Komarov AL, Panchenko EP, Dobrovolsky AB et al. D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease. Eur Heart J 2002; 23: 1309–16.
26. Воробьева Н.М., Панченко Е.П., Добровольский А.Б. и др. Повышение Д-димера у больных сердечно-сосудистыми заболеваниями без тромбоэмболических осложнений: с чем это связано и что делать? Ангиология и сосудистая хирургия. 2010; 16 (4): 34–42.
27. Di Nisio M, Squizzato A, Rutjes AWS et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 5: 296–304.
28. Lowe GDO, Rumley A, Sweetnam PM et al. Fibrin D-dimer, Markers of Coagulation Activation and the Risk of Major Ischaemic Heart Disease in the Caerphilly Study. Thromb Haemost 2001; 85: 822–7.
29. Woodward M, Rumley A, Welsh P et al. A comparison of the associations between seven hemostatic or inflammatory variables and coronary heart disease. J Thromb Haemost 2007; 5: 1795–800.
Авторы
А.Б.Добровольский*1, Е.В.Титаева1, Е.Б.Яровая2, А.Н.Сторожилова1, Ю.В.Жернакова1, Е.В.Ощепкова1, Е.П.Панченко1, И.А.Трубачева3, В.Н.Серебрякова3, В.С.Кавешников3, И.Е.Чазова1, Р.С.Карпов3
1 ФГБУ Российский кардиологический научно-производственный комплекс Минздрава России, Москва
2 Московский государственный университет им. М.В.Ломоносова, Москва
3 ФГБУ НИИ кардиологии СО РАМН, Томск
*abdobrovolsky@inbox.ru
*abdobrovolsky@inbox.ru
1 ФГБУ Российский кардиологический научно-производственный комплекс Минздрава России, Москва
2 Московский государственный университет им. М.В.Ломоносова, Москва
3 ФГБУ НИИ кардиологии СО РАМН, Томск
*abdobrovolsky@inbox.ru
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*abdobrovolsky@inbox.ru
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