Fibrinogen and AER are major independent predictors of 11-year cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study

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)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001) a population-based cohort of 1,565 patients was regularly examined, and measurements of HbA 1 c 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 HbA 1 c 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 shortterm 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 followup. 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 cardiovasvascular 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.

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

“…It has been previously reported that type 2 diabetic patients are characterised by elevated fibrinogen synthesis and plasma levels [5,6]. Our data confirm this observation and demonstrate that LPD is able to reduce ASR of fibrinogen, although it did not significantly reduce fibrinogen FSR.…”

“…Once patients with microalbuminuria progress to macroalbuminuria (overt nephropathy), they are likely to progress to end-stage renal disease [3]. Diabetic nephropathy is often associated with low-grade inflammation [4], hyperfibrinogenaemia [5], dyslipidaemia and high incidence of cardiovascular morbidity and mortality [6,7].…”

Effect of age on the association of non-high-density-lipoprotein cholesterol and apolipoprotein B with cardiovascular mortality in a Mediterranean population with type 2 diabetes: the Casale Monferrato study

“…Models included conventional risk factors (age, sex, smoking, hypertension, CHD), novel risk factors (AER, fibrinogen) and cumulative individual average HbA 1c during follow-up (time-dependent variable). The HRs were also adjusted for referring physician, as previous analyses of the Casale Monferrato cohort identified this as a significant predictor of mortality [24]. Given the time scale, all the models were also adjusted for known duration of diabetes.…”

“…This cohort has been followed prospectively to determine 11-year mortality from all causes and from cardiovascular disease [22][23][24]. As the association of the ApoB:ApoA-I ratio has not been studied in a population-based cohort of people with diabetes, the aims of the analysis reported here were: (1) to investigate the association between plasma lipids, lipoprotein lipids and apolipoprotein with mortality from cardiovascular disease; and (2) to assess whether age modifies any of these relationships.…”

Pulse pressure and systolic night–day ratio interact in prediction of macrovascular disease in patients with type 2 diabetes mellitus

“…[1][2][3] Hence, identification of markers of increased risk for development of cardiovascular disease (CVD), that add to established risk parameters for CVD such as smoking, 4 cholesterol level, 5 albuminuria 6,7 and creatinine level, 8 is important.…”