Objective Type 2 diabetic patients have an increased arterial stiffness and a very high risk of cardiovascular death. The present study investigated the relationship between pulse pressure, an indicator of vascular stiffness, and risk of cardiovascular mortality among type 2 diabetic and non-diabetic individuals. Second, we determined the relationship between pulse pressure and its main determinant (i.e. age), and the influence of diabetes and mean arterial pressure on this relationship. Design and methodsWe studied a cohort of 2484 individuals including 208 type 2 diabetic patients. Mean age and median follow-up for non-diabetic and diabetic individuals, respectively, were 61 and 66 years, and 8.8 and 8.6 years. One-hundred and sixteen non-diabetic and 34 diabetic individuals died of cardiovascular causes. Relative risks of cardiovascular mortality were estimated by Cox proportional hazards regression adjusted for age, gender and mean arterial pressure.Results Pulse pressure was associated with cardiovascular mortality among the diabetic, but not among the non-diabetic individuals [adjusted relative risk (95% confidence interval) per 10 mmHg increase, 1.27 (1.00-1.61) and 0.98 (0.85-1.13), P interaction 0.07]. Further adjustment for other risk factors gave similar results. The association, at baseline, between age and pulse pressure was dependent on the presence of diabetes (P interaction 0.03) and on the mean arterial pressure (P interaction < 0.001) (i.e. there was a stronger association when diabetes was present and when mean arterial pressure was higher).Conclusions We conclude that, in type 2 diabetes, pulse pressure is positively associated with cardiovascular mortality. The association between age and pulse pressure is influenced by the presence of type 2 diabetes and by the height of the mean arterial pressure. These findings support the concept of accelerated vascular aging in type 2 diabetes.

Abstract-Homocysteine is associated with atherothrombotic disease, which may be mediated through associations of homocysteine levels with blood pressure, endothelial function, or arterial stiffness. In a placebo-controlled, randomized clinical trial, we measured blood pressure, brachial artery endothelium-dependent vasodilation, and common carotid artery stiffness in 158 clinically healthy siblings of patients with premature atherothrombotic disease at baseline and after 1 and 2 years of homocysteine-lowering treatment with folic acid (5 mg) plus pyridoxine (250 mg). Intention-to-treat analyses limited to participants (nϭ130) who underwent at least 1 measurement after the baseline visit showed that compared with placebo, treatment with folic acid plus pyridoxine was associated with a 3.7-mm Hg (95% CI Ϫ6.8 to Ϫ0.6 mm Hg) lower systolic and a 1.9-mm Hg (95% CI Ϫ3.7 to Ϫ0.02 mm Hg) lower diastolic blood pressure over the 2-year trial period. Together with the decreased occurrence of abnormal exercise electrocardiography tests reported previously, our results support the hypothesis that homocysteine-lowering treatment with folic acid plus pyridoxine has beneficial vascular effects. Because no effects could be demonstrated on brachial artery endotheliumdependent vasodilation or on common carotid artery stiffness, the present study does not support the hypothesis that the cardiovascular effects of homocysteine are mediated through these factors, at least in clinically healthy individuals.

Background Decreased large artery function, as reflected by increased brachial artery pulse pressure and increased carotid artery diameter and stiffness, may contribute to the increased mortality risk that is observed in subjects with impaired glucose tolerance. We therefore investigated the association between brachial artery pulse pressure and carotid artery diameter and stiffness, which are estimates of central artery stiffness and arterial remodelling, respectively, and mortality in subjects with a recent history of impaired glucose tolerance.

In subjects with type 2 diabetes mellitus, insulin resistance and the use of alcohol were associated with increased arterial stiffness, which supports the hypothesis that increased arterial stiffness can act as a mediating factor in the association between type 2 diabetes mellitus and increased risk of atherothrombotic disease. We found no evidence for an association between fasting or postprandial triglyceridaemia and arterial stiffness.

Brachial artery pulse pressure is a predictor of (cardiovascular) morbidity, but its determinants in individuals with Type II diabetes and untreated mild hypertension have not been elucidated. We therefore cross-sectionally investigated determinants of brachial artery mean 24 h pulse pressure in 60 individuals (40 males; age, mean +/- S.D., 57.8 +/- 7.5 years) with Type II diabetes [median diabetes duration (interquartile range), 6.3 (3.6-10.1) years] and untreated mild hypertension [sitting blood pressure >140/90 mmHg and <190/120 mmHg (mean of two consecutive auscultatory office measurements after 5 min of rest)]. We measured (1) three potential determinants reflecting different aspects of central artery stiffness [the overall systemic arterial compliance, the aortic augmentation index and 1/(regional carotido-femoral transit time)], (2) structural and functional changes of the circulatory system often observed in Type II diabetes, and (3) diabetes-associated metabolic variables. After adjustment for age, gender and mean arterial pressure, brachial artery pulse pressure was associated with autonomic function [standardized regression coefficient (beta), -0.27 (P=0.01)], blood pressure decline during sleep [standardized beta, -0.32 (P=0.002)], fasting glucose concentration [standardized beta, 0.26 (P=0.01)], HbA(1c) concentration [standardized beta, 0.27 (P=0.003)] and diabetes duration [standardized beta, 0.28 (P=0.002)] in linear regression analyses. In a combined multivariate model, brachial artery pulse pressure was independently determined by gender [1=male, 2=female; standardized beta, 0.24 (P=0.01)], diabetes duration [standardized beta, 0.18 (P=0.03)], mean arterial pressure [standardized beta, 0.32 (P=0.002)], systemic arterial compliance [standardized beta, -0.23 (P=0.02)] and fasting glucose concentration [standardized beta, 0.20 (P=0.02)]. Aortic augmentation index and 1/(carotido-femoral transit time) were not independently associated with pulse pressure. In conclusion, in individuals with Type II diabetes and untreated mild hypertension, brachial artery pulse pressure is determined mainly by proximal aortic stiffness in a way which is not strongly influenced by peripheral pulse wave reflection. Approx. 60% of the variance in brachial artery pulse pressure could be explained by potentially modifiable determinants.