Fibrinogen and AER Are Major Independent Predictors of 11-year Cardiovascular Mortality in Type 2 Diabetes: the Casale Monferrato Study

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2005 Feb 8

PMID 15696295

Citations 16

Authors

G Bruno

F Merletti

A Biggeri

G Bargero

S Ferrero

G Pagano

P Cavallo-Perin

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Fibrinogen and elevated AER increase cardiovascular mortality, but few data are available in the type 2 diabetic population. We have conducted an 11-year follow-up study of the Casale Monferrato cohort to assess: (1) the long-term predictive role of AER independently of conventional risk factors; (2) the shape of its relationship with cardiovascular mortality; and (3) whether fibrinogen has a predictive effect independent of the increased cardiovascular risk associated with nephropathy.

Methods: During the follow-up period (1991-2001) a population-based cohort of 1,565 patients was regularly examined, and measurements of HbA1c were centralised. Multivariate Cox proportional hazards modelling was employed to assess the role of fibrinogen and AER as predictors of all-cause and cardiovascular mortality, independently of baseline variables and individual cumulative average values of HbA1c during follow-up.

Results: In 10,890.2 person-years of observations, 685 deaths were identified, giving an all-cause mortality rate of 63.4 per 1,000 person-years (95% CI 58.8-68.3). In Cox regression analyses, the strongest predictor of cardiovascular mortality was macroalbuminuria (relative risk 2.18, 95% CI 1.62-2.94), which was mainly associated with a high risk of short-term mortality. No increased risk was evident until the upper microalbuminuric range of AER values. Plasma fibrinogen was also a major independent predictor, and its role was not modified by AER, or by the exclusion of subjects developing chronic renal failure or diabetic nephropathy during follow-up.

Conclusions/interpretation: The results indicate that: (1) AER is the main independent predictor of 11-year cardiovascular mortality; (2) this effect is mainly evident in the upper range of microalbuminuria and in macroalbuminuria; and (3) fibrinogen has an independent effect on cardiovascular mortality, but no synergistic effect with AER, suggesting that both endothelial dysfunction and chronic inflammation are involved in the excess cardiovascular mortality of type 2 diabetic patients.

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References

Bruno G, LaPorte R, Merletti F, Biggeri A, McCarty D, Pagano G . National diabetes programs. Application of capture-recapture to count diabetes?. Diabetes Care. 1994; 17(6):548-56. DOI: 10.2337/diacare.17.6.548. View

Yuyun M, Dinneen S, Edwards O, Wood E, Wareham N . Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy. Diabet Med. 2003; 20(4):277-82. DOI: 10.1046/j.1464-5491.2003.00940.x. View

Gerstein H, Mann J, Yi Q, Zinman B, Dinneen S, Hoogwerf B . Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001; 286(4):421-6. DOI: 10.1001/jama.286.4.421. View

Bosnyak Z, Forrest K, Maser R, Becker D, Orchard T . Do plasminogen activator inhibitor (PAI-1) or tissue plasminogen activator PAI-1 complexes predict complications in Type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study. Diabet Med. 2003; 20(2):147-51. DOI: 10.1046/j.1464-5491.2003.00898.x. View

Hanley A, Festa A, DAgostino Jr R, Wagenknecht L, Savage P, Tracy R . Metabolic and inflammation variable clusters and prediction of type 2 diabetes: factor analysis using directly measured insulin sensitivity. Diabetes. 2004; 53(7):1773-81. DOI: 10.2337/diabetes.53.7.1773. View

Bruno G, Cavallo-Perin P, Bargero G, Borra M, Derrico N, Macchia G . Hyperfibrinogenemia and metabolic syndrome in type 2 diabetes: a population-based study. Diabetes Metab Res Rev. 2001; 17(2):124-30. DOI: 10.1002/1520-7560(2000)9999:9999<::aid-dmrr166>3.0.co;2-g. View

Greaves M, Malia R, Goodfellow K, Mattock M, Stevens L, Stephenson J . Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study. Diabetologia. 1997; 40(6):698-705. DOI: 10.1007/s001250050736. View

Ritz E . Albuminuria and vascular damage--the vicious twins. N Engl J Med. 2003; 348(23):2349-52. DOI: 10.1056/NEJMe030066. View

Tracy R, Arnold A, Ettinger W, Fried L, Meilahn E, Savage P . The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study. Arterioscler Thromb Vasc Biol. 1999; 19(7):1776-83. DOI: 10.1161/01.atv.19.7.1776. View

10.

Dinneen S, Gerstein H . The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med. 1997; 157(13):1413-8. View

11.

Yano K, Grove J, Chen R, Rodriguez B, Curb J, Tracy R . Plasma fibrinogen as a predictor of total and cause-specific mortality in elderly Japanese-American men. Arterioscler Thromb Vasc Biol. 2001; 21(6):1065-70. DOI: 10.1161/01.atv.21.6.1065. View

12.

Bruno G, Merletti F, Biggeri A, Bargero G, Ferrero S, Pagano G . Progression to overt nephropathy in type 2 diabetes: the Casale Monferrato Study. Diabetes Care. 2003; 26(7):2150-5. DOI: 10.2337/diacare.26.7.2150. View

13.

Bruno G, Cavallo-Perin P, Bargero G, Borra M, Derrico N, Pagano G . Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 125(8):653-7. DOI: 10.7326/0003-4819-125-8-199610150-00005. View

14.

Agewall S, Wikstrand J, Ljungman S, Fagerberg B . Usefulness of microalbuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Risk Factor Intervention Study Group. Am J Cardiol. 1997; 80(2):164-9. DOI: 10.1016/s0002-9149(97)00312-3. View

15.

Mattock M, Barnes D, Viberti G, Keen H, Burt D, Hughes J . Microalbuminuria and coronary heart disease in NIDDM: an incidence study. Diabetes. 1998; 47(11):1786-92. DOI: 10.2337/diabetes.47.11.1786. View

16.

Chan J, Cheung C, Cheung M, Swaminathan R, Critchley J, Cockram C . Abnormal albuminuria as a predictor of mortality and renal impairment in Chinese patients with NIDDM. Diabetes Care. 1995; 18(7):1013-6. DOI: 10.2337/diacare.18.7.1013. View

17.

Gall M, Borch-Johnsen K, Hougaard P, Nielsen F, Parving H . Albuminuria and poor glycemic control predict mortality in NIDDM. Diabetes. 1995; 44(11):1303-9. DOI: 10.2337/diab.44.11.1303. View

18.

Bruno G, Cavallo-Perin P, Bargero G, Borra M, Derrico N, Macchia G . Cardiovascular risk profile of type 2 diabetic patients cared for by general practitioners or at a diabetes clinic: a population-based study. J Clin Epidemiol. 1999; 52(5):413-7. DOI: 10.1016/s0895-4356(99)00002-5. View

19.

Ostgren C, Lindblad U, Melander A, Rastam L . Survival in patients with type 2 diabetes in a Swedish community: skaraborg hypertension and diabetes project. Diabetes Care. 2002; 25(8):1297-302. DOI: 10.2337/diacare.25.8.1297. View

20.

Kirk A, Mutrie N, Macintyre P, Fisher M . Effects of a 12-month physical activity counselling intervention on glycaemic control and on the status of cardiovascular risk factors in people with Type 2 diabetes. Diabetologia. 2004; 47(5):821-32. DOI: 10.1007/s00125-004-1396-5. View