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von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects : The Hoorn study

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Author: Jager, A. · Hinsbergh, V.W.M. van · Kostense, P.J. · Emeis, J.J. · Yudkin, J.S. · Nijpels, G. · Dekker, J.M. · Heine, R.J. · Bouter, L.M. · Stehouwer, C.D.A.
Institution: Gaubius instituut TNO
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 12, 19, 3071-3078
Identifier: 235264
doi: doi:10.1161/01.ATV.19.12.3071
Keywords: Biology · Acute phase reactant · C-reactive protein · Cardiovascular mortality · Non- insulin-dependent diabetes mellitus · von Willebrand factor · C reactive protein · Acute-Phase Reaction · Aged · C-Reactive Protein · Cohort Studies · Coronary Disease · Diabetes Mellitus, Type 2 · Female · Follow-Up Studies · Humans · Male · Middle Aged · Prospective Studies · Risk Factors · Survival Analysis · von Willebrand Factor


Increased levels of von Willebrand factor (vWf) and C-reactive protein (CRP) predict cardiovascular mortality in selected populations. It is uncertain whether vWf and CRP predict mortality in a general population and whether vWf and CRP predict mortality through similar pathways. This study investigated the association of vWf and CRP with cardiovascular and all-cause mortality among diabetic and nondiabetic subjects. An age-, sex-, and glucose tolerance-stratified sample (n=631) of a population-based cohort aged 50 to 75 years was followed prospectively for 5 years. After 5 years of follow-up, 58 subjects had died (24 of cardiovascular causes). vWf (>1.56 IU/mL) and CRP (>2.84 mg/L) levels in the upper tertile were associated with, respectively, a 3- and 2-fold increase in cardiovascular mortality after adjustment for age, sex, and glucose tolerance status. Analyses in nondiabetic and diabetic subjects separately gave similar results. After further adjustment for hypertension, levels of HDL cholesterol and triglyceride, smoking habits, ischemic heart disease, and peripheral arterial disease, the relative risks (RRs) were 3.0 (95% CI 1.2 to 7.9) for vWf and 1.4 (95% CI 0.6 to 3.5) for CRP. When both vWf and CRP were included in the latter multivariate analysis, the RRs were 3.0 (95% CI 1.1 to 7.9) for vWf and 1.3 (95% CI 0.5 to 3.4) for CRP. The association between vWf and risk of cardiovascular mortality was independent of blood group (O versus non-O) and, moreover, similar among subjects with different blood groups. Repeating the analyses for all-cause mortality gave similar results for CRP. For vWf, the RR was 2.0 (95% CI 1.1 to 3.5) after adjustment for all other risk factors. Increased levels of vWf are independently associated with cardiovascular and all-cause mortality in both diabetic and nondiabetic subjects. The association between increased levels of CRP and cardiovascular mortality was partly explained by other risk factors. Mutual adjustment of vWf and CRP did not markedly change the results, favoring the hypothesis that vWf and CRP predict mortality through different pathways.