IMPACT OF THE INFLAMMATORY AND ISCHEMIC HEART DISEASE MARKERS INTO THE OVERALL CARDIOVASCULAR MORTALITY IN SENILE CITIZENS OF A LARGE CITY (THE DATA FROM SAHR TRIAL)
https://doi.org/10.15829/1560-4071-2015-6-7-13
Abstract
Aim. To study the associations of inflammation markers (hsCRP, IL-6, FG, leucocytes, ESR) with coronary heart disease (CHD) and their impact on overall cardiovascular mortality in old citizens of Moscow.
Material and methods. We used the data from prospective cohort study “Stress, Ageing and Health in Russia” (SAHR) — a representative selection from non-organized inhabitants of Moscow citizens from 55 years old. The duration of the study has been 5 years (since June 2006 to May 2011) at FSBI SSICPM of the Healthcare ministry and included 1871 persons. All participants underwent standard questioning. Into analysis we included gender, age, educational level, classic risk factors. For the assessment of current subclinical inflammation we used high-sensititvity C-reactive protein (hsCRP), interleucine 6 (IL-6), fibrinogen (FG), leucocytes, erythrocyte sedimentation rate (ESR). For CHD screening, we used standard ROse questionnaire and ECG pattern by Minnesota coding. Mortality was evaluated under the continuous death cases registry. At the beginning of 2014 totally 314 fatal cases registered, including 186 of CVD.
Results. There were significant associations more prominent in women, of the smoking in anamnesis, increased BP levels, obesity and CHD, diagnosed at a strict multifactorial analysis. Among inflammation markers, the significant correlation with CHD showed hsCRP and IL-6. In monofactor analysis, correct just for the age and gender, all studied markers significantly associated with total and cardiovascular mortality. In multidimensional model of proportional risk, that included gender, age, CHD by strict or mild criteria, all risk factors and al inflammation markers, remained statistically significant by their impact on mortality from all causes and from CVD, except gender, age and strict-criteria CHD (HR — 95% CI: 1,5-1,15;1,96, р=0,0029 and 2,0-1,41;2,88, р=0,0001, resp.), smoking, hsCRP (HR — 95% CI: 1,031,01;1,05, р=0,0002 and 1,03-1,01;1,05, р=0,007, resp.) and IL-6 (HR — 95% CI: 1,02-1,0;1,03, р=0,04 и 1,02-1,0;1,04, р=0,022, resp.).
Conclusion. HsCRP, IL-6 and CHD by strict criteria, even after correction on gender, age and traditional risk factors, significantly correlate with total and cardiovascular mortality in men and women of 55 y.o. and older.
About the Authors
S. A. ShalnovaRussian Federation
S. E. Evstifeeva
Russian Federation
A. D. Deev
Russian Federation
V. A. Metelskaya
Russian Federation
A. V. Kapustina
Russian Federation
Competing Interests: Старший научный сотрудник отдела эпидемиологии ХНИЗ
G. A. Muromtseva
Russian Federation
Yu. A. Balanova
Russian Federation
E. M. Tuaeva
Russian Federation
A. E. Imajeva
Russian Federation
N. V. Kiseleva
Russian Federation
Competing Interests: State Scientific-Research Centre for Prevention Medicine, Moscow
M. A. Shkolnikova
Russian Federation
References
1. Karpov Yu.A, Sorokin EV., Fomicheva OA. Inflammation and atherosclerosis: scope of the problem and unresolved issues. Heart 2004; 4(2):190-2. Russian (Карпов Ю.А., Сорокин Е.В., Фомичева О.А. Воспаление и атеросклероз: состояние проблемы и нерешенные вопросы. Сердце 2004; 4(2): 190-2).
2. Tracy RP. Inflammation in cardiovascular disease. Circulation 1998; 97: 2000-02.
3. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115-26.
4. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) European Heart Journal 2012; 33: 1635-701.
5. Shkolnikova M, Shalnova S, Shkolnikov VM, et al. Biological mechanisms of disease and death in Moscow: rationale and design of the survey on Stress Aging and Health in Russia (SAHR). BMC Public Health 2009; 9: 293. Available from: http://www.biomedcentral. com/1471-2458/9/293
6. Rose G, Blackburn H, Gillum R, et al. Cardiovascular survey methods. In WHO Monograph Series No. 56. 2nd edition. Geneva: World Health Organization 1982: 149-72.
7. Winston H, Koenig W, Frohlich M. Immunoradiometric Assay of Circulating C-Reactive Protein: Age-related Values in the Adult General Population. Clinical Chemistry 2000; 46(7): 934-8.
8. Abernathy JR, Thorn GB, Trobaugh LG, et al. Prevalence of ischemic resting and stress electrocardiographic abnormalities and angina among 40to 59-year-old men in selected U.S. and U.S.S.R. populations. Circulation 1988; 2(77): 270-8.
9. Shalnova S. A., Deev A. D., Shestov D. B., et al. Prognostic assessment of epidemiological characteristics of ischemic heart disease. Kardiologija 1997; 9: 49-54. Russian (Шальнова С.А., Деев А.Д., Шестов Д.Б. и др. Прогностическая оценка эпидемиологических характеристик ишемической болезни сердца. Кардиология 1997; 9: 49-54).
10. SAS/STAT User’s Guide, Version 6, Fourth Edition, V.1 & 2, SAS Institute Inc., Cary, NC, USA, 1990.
11. European guidelines on cardiovascular disease and prevention in clinical practice. Eur J Cardiovascular Prevent Rehabil 2003; 10(1): 1-78.
12. Strandberg TE, Tilvis RS. C-reactive protein. Cardiovascular risk factors, and mortality in the prospective study in the elderly. Arterioscler Thromb Vasc Biol. 2000; 20: 1057-60.
13. Kuller LH, Tracy RP, Shaten J, et al. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. Am J Epidemiol 1996; 144: 537-47.
14. Frohlich M, Sund M, Lowel H, et al. Independent association of various smoking characteristics with markers of systemic inflammation in men. Results from a representative sample of the general population (MONICA Augsburg Survey 1994/95). Eur Heart J 2003; 24: 1365-72.
15. Memon L, Spasojevic-Kalimanovska V, et al. Association of C-reactive protein with the Presense and Extent of Angiographically Verified Coronary Artery Disease. Tohoku J Exp Med 2006; 209: 197-206.
16. Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000; 321: 199-204.
17. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836-43.
18. Harb TS, Zareba W, Moss AJ, et al. Association of C-reactive protein and serum amyloid А with recurrent coronary events in stable patients after healing of acute myocardial infarction. Am J Cardiol 2002; 89: 216-21.
19. Danesh J, Phil D, Wheeler JG, et al. C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease. N Engl J Med 2004; 350: 1387-97.
20. Ridker P, Rifai N, Rose L, et al. Comparison of c-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347: 1557-65.
21. Berger JS, Jordan CO, Lloyd-Jones D, et al. Screening for cardiovascular risk in asymptomatic patients. J Am Coll Cardiol 2010; 55: 1169-77.
22. Nazarenko GI., Kiskun AA. Clinical evaluation of laboratory results. Moscow: Izdatel’stvo “Medicine”; 2006. Russian (Назаренко Г. И., Кишкун А.А. Клиническая оценка результатов лабораторных исследований. М.: Издательство “Медицина”; 2006).
23. Martins TB, Anderson JL, Muhlestein JB, et al. Risk factor analysis of plasma cytokines in patient with coronary artery disease by a multiplexed fluorescent immunoassay. Am J Clin Pathol 2006; 125: 906-13.
24. Serebrennikov SN., Seminsky JJ. The Role of cytokines in inflammatory process. Siberian Med. J 2008; 8: 5-9. Russian (Серебренников С.Н., Семинский И.Ж. Роль цитокинов в воспалительном процессе. Сибирский медицинский журнал 2008; 8: 5-9).
25. Tanindi A, Sahinarslan A, Elbeg S, et al. Relationship Between MMP-1, MMP-9, TIMP1, IL-6 and Risk Factors, Clinical Presentation, Extent and Severity of Atherosclerotic Coronary Artery Disease. Open. Cardiovasc. Med. J. 2011; 5: 110-6.
26. Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med 2008; 5(4): 600-10.
27. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101(15): 1767-72.
28. Volpato S, Guralnik JM, Ferrucci L, et al. Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women’s health and aging study. Circulation 2001; 103(7): 947-53.
29. Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and Creactive protein levels with mortality in the elderly. Am J Med 1999; 106(5): 506-12.
30. Lee KWJ, Hill JS, Walley KR, et al. Relative value of multiple plasma biomarkers as risk factors for coronary artery disease and death in an angiography cohort. CMAJ 2006; 174 :461-6.
31. Lai CL, Ji YR, Liu XH, et al. Relationship between coronary atherosclerosis plaque characteristics and high sensitivityC-reactive proteins, interleukin-6. Chin. Med. J. Engl. 2011; 124(16): 2452-6.
32. Di Minno G, Mancini M. Measuring plasma fibrinogen to predict stroke and myocardial infarction. Arteriosclerosis 1990; 10(1): 1-7.
33. Meade TW, Brozovic M, Chakrabarty RR, et al. Hemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 2: 533-7.
34. Fibrinogen Studies Collaboration. Plasma Fibrinogen Level and the Risk of Major Cardiovascular Diseases and Nonvascular Mortality. An Individual Participant Metaanalysis. JAMA 2005; 294: 1799-809.
35. Kannel WB, D’Agostino RB, Belanger AJ. Fibrinogen, cigarette smoking and risk of cardiovascular disease: Insights from the Framingham Study. Am Heart J 1987; 113: 1006-10.
36. Syrjanen J, Valitonen VV, Iivanainen M, et al. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients. Br. Med. J 1988, 296: 1156-60.
37. Shevchenko OP. Characteristics and clinical significance of acute phase proteins of inflammation. Laboratory diagnosis. edit. Dolgov VV., Shevchenko OP. Moscow: Izdatel’stvo “Reaffirm”; 2005: 137-43. Russian (Шевченко О.П. Характеристика и клиническое значение белков острой фазы воспаления. Лабораторная диагностика под ред. Долгов В.В., Шевченко О.П. М.: Издательство “Реафарм”; 2005: 137-43).
38. Giesen PLA, Rauch U, Bohrman В, et al. Blood-born tissue factor: another view of thrombosis PNAS USA 1999; 96: 2311-15.
39. Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998; 97: 2007-11.
40. Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, Pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998; 98: 839-44.
41. Biasucci LM, Liuzzo G, Grillo RL, et al. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999; 99: 855-60.
Review
For citations:
Shalnova S.A., Evstifeeva S.E., Deev A.D., Metelskaya V.A., Kapustina A.V., Muromtseva G.A., Balanova Yu.A., Tuaeva E.M., Imajeva A.E., Kiseleva N.V., Shkolnikova M.A. IMPACT OF THE INFLAMMATORY AND ISCHEMIC HEART DISEASE MARKERS INTO THE OVERALL CARDIOVASCULAR MORTALITY IN SENILE CITIZENS OF A LARGE CITY (THE DATA FROM SAHR TRIAL). Russian Journal of Cardiology. 2015;(6):7-13. (In Russ.) https://doi.org/10.15829/1560-4071-2015-6-7-13