C-Reactive Protein and 5-Year Survival in Type 2 Diabetes

Abstract

OBJECTIVETo determine to what extent plasma C-reactive protein (CRP) values influence 5-year all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of albumin excretion rate (AER) and other cardiovascular risk factors, and its incremental usefulness for predicting individual risk of mortality.RESEARCH DESIGN AND METHODSMeasurements of CRP were performed in 2,381 of 3,249 (73.3%) subjects as part of the population-based Casale Monferrato Study. Its association with 5-year all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. The C statistic and measures of calibration and global fit were also assessed.RESULTSResults are based on 496 deaths in 11.717 person-years of observations (median follow-up 5.4 years). With respect to subjects with CRP ≤3 mg/l, those with higher values had an adjusted hazard ratio (HR) of 1.51 (95% CI 1.18–1.92) for all-cause mortality and 1.44 (0.99–2.08) for cardiovascular mortality. In normoalbuminuric subjects, respective HRs of CRP were 1.56 (1.13–2.15) and 1.65 (1.00–2.74), AER being neither a modifier nor a confounder of CRP association. In analysis limited to diabetic subjects without cardiovascular disease (CVD), adjusted HRs were 1.67 (1.24–2.24) for all-cause mortality and 1.36 (0.83–2.24) for cardiovascular mortality. The improvement in individual risk assessment was marginal when measured with various statistical measures of model discrimination, calibration, and global fit.CONCLUSIONSCRP measurement is independently associated with short-term mortality risk in type 2 diabetic individuals, even in normoalbuminuric subjects and in those without a previous diagnosis of CVD. Its clinical usefulness in individual assessment of 5-year risk of mortality, however, is limited.

High‐sensitivity C‐reactive protein, low‐density lipoprotein cholesterol and cardiovascular outcomes in patients with type 2 diabetes in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial

“…In contrast, several prospective cohort studies have shown that individuals with higher CRP levels were at risk of future CV disease, including patients with type 2 diabetes 6, 7, 8, 9. In a population‐based Italian cohort, followed for 5 years, higher CRP values (>3 mg/L) were associated with increased overall and CV mortality in patients with type 2 diabetes after adjusting for conventional CV risk factors 6.…”

“…To date, several prospective studies have examined the role of hsCRP in predicting future CV morbidity and mortality in stable patients with type 2 diabetes mellitus, with varying results 6, 7, 8, 9, 10, 11, 12. The aim of our study was to determine whether the baseline hsCRP level is predictive of the risk of major adverse cardiovascular events (MACE), a composite of cardiovascular death, non‐fatal myocardial infarction and stroke, in patients at high risk of CV disease, with type 2 diabetes and recent ACS, who were enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial 13.…”

Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment

“…Moreover, CRP directly facilitates the development of cardiovascular disease by decreasing nitric oxide synthesis and inducing adhesion molecule expression in human endothelial cells [17,18]. Recently, CRP was reported to be independently associated with short-term mortality risk in type 2 diabetes mellitus patients [19]; and several studies have shown that pioglitazone reduces plasma CRP levels [3][4][5][6][7][8][9][10][11][12][13]. Moreover, 16 weeks of pioglitazone treatment decreased CRP levels by 42% in type 2 diabetes mellitus patients [12]; and pioglitazone further reduced CRP in patients with hypertension and diabetes who were receiving angiotensin II receptor blockers [5].…”

“…Moreover, CRP directly facilitates the development of cardiovascular disease by hindering nitric oxide synthesis and inducing adhesion molecule expression in human endothelial cells [17,18]. Recently, CRP was reported to be independently associated with short-term mortality risk in type 2 diabetes mellitus patients [19]. In addition, Williams et al [20] reported that the levels of systolic blood pressure, CRP, and apolipoprotein B are higher in diabetic women than in diabetic men; and such conditions result in a loss of cardiovascular protection.…”

Correlation of CRP level with glycemic control in diabetic foot patients and its sequelae

“…[6][7][8][9] Growing evidence indicates that diabetic individuals have higher concentrations of CRP than nondiabetic individuals, suggesting an increased role of inflammation in the accelerated atherosclerosis seen in these patients. [10][11][12][13][14] Diabetes is a serious public health problem that has been increasing exponentially across the globe. The risk of CVD is two-to four times higher in type 2 diabetics and >50% of all diabetic patients die of CVD.…”