Annemarie Becker

Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments

We aimed to investigate the prevalence of depression in cancer patients assessed by diagnostic interviews and self‐report instruments, and to study differences in prevalence between type of instrument, type of cancer and treatment phase.

Endothelial Dysfunction Contributes to Renal Function–Associated Cardiovascular Mortality in a Population with Mild Renal Insufficiency: The Hoorn Study

Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n = 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 +/- 12 ml/min per 1.73 m(2)) and independently associated with von Willebrand factor (standardized beta -0.09; 95% confidence interval [CI] -0.18 to -0.002; P < 0.05), soluble vascular cell adhesion molecule-1 (standardized beta -0.14; 95% CI -0.22 to -0.05; P < 0.01), and albumin-creatinine ratio (standardized beta -0.15; 95% CI -0.23 to -0.08; P < 0.001) but not with markers of inflammatory activity. Renal function was inversely associated with cardiovascular and all-cause mortality. The relative risk for cardiovascular mortality but not all-cause mortality associated with renal function decreased from 1.22 to 1.12 per 5 ml/min per 1.73 m(2) decrease of eGFR after adjustment for markers of endothelial dysfunction. In conclusion, endothelial dysfunction was related to renal function and contributed to the excess in cardiovascular mortality in this population-based cohort with mild renal insufficiency.

Cardiovascular events in type 2 diabetes : comparison with nondiabetic individuals without and with prior cardiovascular disease. 10-year follow-up of the Hoorn Study

AIMS We questioned whether prior cardiovascular disease has the same impact on risk of cardiovascular events as type 2 diabetes, and whether this differed between men and women. METHODS AND RESULTS To address these issues we compared the 10-year risk of cardiovascular events among 208 Caucasian individuals with diabetes to that of 2253 Caucasian individuals without diabetes, in a population-based cohort study. Gender significantly modified the association between type 2 diabetes and cardiovascular events (p=0.01). The hazard ratio of cardiovascular events associated with the presence of diabetes was higher in women (adjusted hazard ratio, 1.8; 95% CI, 1.2 to 2.7) than in men (adjusted hazard ratio, 1.3; 0.9 to 2). As compared to men without diabetes but with prior cardiovascular disease, risk of cardiovascular events was significantly lower in men with diabetes but without prior cardiovascular disease (adjusted hazard ratio, 0.5; 0.3 to 0.9). In contrast, this risk was equal in women with diabetes but without prior cardiovascular disease and women without diabetes but with prior cardiovascular disease (adjusted hazard ratio, 1.0; 0.6 to 1.7; P for interaction between gender and diabetes=0.05). CONCLUSIONS Women with diabetes but without prior cardiovascular disease have a risk of cardiovascular events that is similar to that of women without diabetes but with prior cardiovascular disease, whereas in men the presence of prior cardiovascular disease conferred a higher risk. These data emphasise the necessity of aggressive treatment of cardiovascular risk factors in women with type 2 diabetes.

Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes

Abstract.  Becker A, Kostense PJ, Bos G, Heine RJ, Dekker JM, Nijpels G, Bouter LM, Stehouwer CDA (VU University Medical Center, Amsterdam, the Netherlands). Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes. J Intern Med 2003; 253: 293–300.

S‐adenosylhomocysteine and the ratio of S‐adenosylmethionine to S‐adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations

Background It is unclear whether homocysteine itself is causal in the pathogenesis of cardiovascular disease. Alternatively or additionally, the association between homocysteine and cardiovascular disease may be because of its metabolic precursor, S‐adenosylhomocysteine, or of the ratio of S‐adenosylmethionine to S‐adenosylhomocysteine. Therefore, it is relevant to know how these moieties are interrelated, and whether, as is the case for homocysteine, they are influenced by blood levels of folate, cobalamin or vitamin B6.

Plasma homocysteine and S-adenosylmethionine in erythrocytes as determinants of carotid intima-media thickness: different effects in diabetic and non-diabetic individuals The Hoorn Study

OBJECTIVE Hyperhomocysteinemia is a risk factor for atherothrombosis. Through unknown mechanisms, individuals with type 2 diabetes appear particularly susceptible. We determined whether components of homocysteine metabolism are associated with intima-media thickness in individuals with and without type 2 diabetes. METHODS AND RESULTS In a cross-sectional design, we studied 231 Caucasian individuals, 60.6% having type 2 diabetes. We measured fasting homocysteine, vitamin B6 and vitamin B12 in plasma, and folate, S-adenosylmethionine and S-adenosylhomocysteine in plasma and erythrocytes. A homocysteine concentration >12 micromol/l was associated with a greater intima-media thickness of +0.07 mm (95% CI, +0.01 to +0.13; P=0.03) among diabetic individuals and of -0.004 mm (95%CI, -0.08 to +0.07; P=0.92) among non-diabetic individuals. An erythrocyte S-adenosylmethionine concentration above >4000 nmol/l was associated with a smaller intima-media thickness of -0.04 mm (95%CI, -0.10 to +0.02; P=0.17) for diabetic individuals versus -0.12 mm (95%CI, -0.20 to -0.36; P=0.005) for non-diabetic individuals. CONCLUSIONS With regard to carotid intima-media thickness, individuals with diabetes appear more susceptible to the detrimental effects of homocysteine than non-diabetic individuals. In addition, diabetic individuals may lack the protective effect on the vascular wall conferred by high concentrations of S-adenosylmethionine. These findings may help explain why hyperhomocysteinemia is an especially strong risk factor for atherothrombosis among individuals with type 2 diabetes.

S-Adenosylmethionine and 5-Methyltetrahydrofolate Are Associated With Endothelial Function After Controlling for Confounding by Homocysteine The Hoorn Study

Objective—To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors. Methods and Results—In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [&mgr;m]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 &mgr;m (21.16; 75.98) and −32.15 &mgr;m (−59.09; −5.20), but high homocysteine was not (−15.11 &mgr;m (−42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors. Conclusions—In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Stepped care targeting psychological distress in head and neck and lung cancer patients: a randomized clinical trial

BackgroundPsychological distress is common in cancer survivors. Although there is some evidence on effectiveness of psychosocial care in distressed cancer patients, referral rate is low. Lack of adequate screening instruments in oncology settings and insufficient availability of traditional models of psychosocial care are the main barriers. A stepped care approach has the potential to improve the efficiency of psychosocial care. The aim of the study described herein is to evaluate efficacy of a stepped care strategy targeting psychological distress in cancer survivors.Methods/designThe study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention programme versus care as usual. Patients treated for head and neck cancer (HNC) or lung cancer (LC) are screened for distress using OncoQuest, a computerized touchscreen system. After stratification for tumour (HNC vs. LC) and stage (stage I/II vs. III/IV), 176 distressed patients are randomly assigned to the intervention or control group. Patients in the intervention group will follow a stepped care model with 4 evidence based steps: 1. Watchful waiting, 2. Guided self-help via Internet or a booklet, 3. Problem Solving Treatment administered by a specialized nurse, and 4. Specialized psychological intervention or antidepressant medication. In the control group, patients receive care as usual which most often is a single interview or referral to specialized intervention. Primary outcome is the Hospital Anxiety and Depression Scale (HADS). Secondary outcome measures are a clinical level of depression or anxiety (CIDI), quality of life (EQ-5D, EORTC QLQ-C30, QLQ-HN35, QLQ-LC13), patient satisfaction with care (EORTC QLQ-PATSAT), and costs (health care utilization and work loss (TIC-P and PRODISQ modules)). Outcomes are evaluated before and after intervention and at 3, 6, 9 and 12 months after intervention.DiscussionStepped care is a system of delivering and monitoring treatments, such that effective, yet least resource-intensive, treatment is delivered to patients first. The main aim of a stepped care approach is to simplify the patient pathway, provide access to more patients and to improve patient well-being and cost reduction by directing, where appropriate, patients to low cost (self-)management before high cost specialist services.Trial registrationNTR1868

Epidemiology of Homocysteine as a Risk Factor in Diabetes

Patients with diabetes mellitus are prone to cardiovascular disease, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinemia, may be involved in the atherothrombotic process in these subjects. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. This has been ascribed to hyperfiltration and renal dysfunction or low folate status, respectively. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration has also been shown to be related to macrovascular disease and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may relate to worsening of endothelial dysfunction or structural vessel properties. Because homocysteine and diabetes have an apparent synergistic detrimental vascular effect, patients with diabetes are good candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.

Homocysteine and vascular disease in diabetes: a double hit?

Abstract Cardiovascular disease is a major problem in diabetes, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinaemia, may be related to the development of cardiovascular complications in diabetic individuals. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. Homocysteine levels in diabetes are modulated by hyperfiltration and renal dysfunction, as well as low folate status. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinaemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration is a significant predictor of cardiovascular events and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may be related to worsening of endothelial dysfunction and/or structural vessel properties induced by oxidative stress. Because homocysteine and diabetes have apparent synergistic detrimental vascular effects, patients with diabetes are candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.