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Introduction We evaluated the relationship between adipokine plasma concentrations and body fat distribution and the metabolic syndrome. Methods In a cohort of 1215 patients with clinically manifest vascular disease the relation between subcutaneous adipose tissue, visceral adipose tissue, waist circumference, body mass index and plasma concentrations of adipsin, chemerin, monocyte chemoattractant protein-1, migration inhibitory factor, nerve growth factor, resistin, plasma amyloid A1, adiponectin, leptin, plasminogen activator inhibitor-1 and hepatic growth factor were cross-sectionally assessed with linear regression and adjusted for age and gender. The relation between adipokines and the metabolic syndrome was cross-sectionally evaluated using logistic regression. An adipokine profile was developed to measure the effect of combined rather than single adipokines. Results Adiposity was related to higher nerve growth factor, hepatic growth factor, migration inhibitory factor, leptin and adipsin and with lower chemerin, plasminogen activator inhibitor-1, resistin, plasma amyloid A1 and adiponectin. The strongest positive relations were between body mass index and adipsin (β 0.247; 95% CI 0.137-0.356) and leptin (β 0.266; 95% CI 0.207-0.324); the strongest negative relations were between body mass index and plasma amyloid A1 (β -0.266; 95% CI -0.386 to -0.146) and visceral adipose tissue and adiponectin (β -0.168; 95% CI -0.226 to -0.111). There was no relation between subcutaneous adipose tissue and adipokines. Odds for the metabolic syndrome were higher with each 1 SD higher hepatic growth factor (OR 1.21; 95% CI 1.06-1.38) and leptin (OR 1.26; 95% CI 1.10-1.45) and lower with each 1 SD higher adiponectin (OR 0.73; 95% CI 0.64-0.83) and resistin (OR 0.85; 95% CI 0.74-0.97). The adipokine profile was related to the metabolic syndrome (OR 1.03; 95% CI 1.00-1.06). Conclusion Plasma concentrations of adipokines are related to obesity and body fat distribution. The relation between adipokine concentrations and the metabolic syndrome is independent of visceral adipose tissue.

Background: Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets., Methods: The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents., Results: The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%-28%), varying from <10% in 18% to >30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be <10% in 47% and >30% in 9% of the patients (median, 11%; interquartile range, 7%-17%)., Conclusions: Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk <10%. These data suggest that even with optimal treatment, many patients with vascular disease will remain at >20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need., (© 2016 American Heart Association, Inc.)

Background: Patients with cardiovascular disease might be at increased risk of non-vascular mortality due to shared risk factors. Our aim was to evaluate causes of death and years of life lost (YLL) in patients with different manifestations of vascular disease., Design: The design was a prospective cohort study., Methods: A total of 5911 patients with stable coronary artery disease, cerebrovascular disease, peripheral artery disease (PAD), abdominal aortic aneurysm or polyvascular disease were followed-up for mortality. Cause-specific standardised mortality ratios (SMRs) and YLL, compared to the Dutch population, were estimated. Determinants for cause-specific mortality were evaluated using competing risks models., Results: During a median follow-up of 6.0 years (interquartile range (IQR): 3.1-9.2), 958 (16.2%) patients died. All-cause mortality was increased compared to the general population (SMR: 1.26, 95% confidence interval (CI): 1.18-1.34). Patients with PAD and polyvascular disease were at highest risk, especially for ischaemic heart disease (SMR: 2.52, 95% CI: 1.70-3.60 and SMR: 3.97, 95% CI: 3.18-4.90, respectively). Patients with PAD were at increased risk of dying from cancer (SMR: 1.67, 95% CI: 1.25-2.17). On average, patients with vascular disease of ≥50 years died 7.8 years younger than the general population, with 80% of the excess YLL attributable to cardiovascular disease. In middle-aged patients the excess YLL were about 10 years, of which 24% were lost due to cancer. Important determinants for mortality were male gender, smoking, physical inactivity, renal insufficiency and polyvascular disease., Conclusions: Patients with manifest vascular disease are at increased risk of both cardiovascular and cancer mortality, particularly patients with PAD or polyvascular disease. On average, patients with vascular disease of ≥50 years die 7.8 years younger than the general population., (© The European Society of Cardiology 2015.)

Introduction: In patients with CAD, moderate levels of leisure time physical activity are associated with lower risk of mortality. However, less is known about the effects in patients with vascular disease other than CAD. In this study, we examined the association between physical activity and risk of future vascular events and all-cause mortality in patients with vascular disease or risk factors and investigated whether these associations were similar across the different manifestations of vascular disease., Methods: A total of 9942 consecutive patients with various manifestations of vascular disease or risk factors enroled in the Second Manifestations of ARTerial disease study were included. The amount of physical activity was assessed at baseline in MET-hours per week., Results: The study population (mean age, 56.7 yr; male, 67%) had a median level of physical activity of 17.4 MET·h·wk(-1). During a median follow-up of 6.7 yr, 1224 vascular events and 1353 cases of all-cause mortality were recorded. Cox regression analyses adjusted for age, sex, smoking, and current alcohol consumption showed that higher levels of physical activity were associated with reduced risk of vascular events (quartile 4 vs quartile 1; hazard ratio, 0.68 (95% confidence interval, 0.58-0.79)) and all-cause mortality (hazard ratio, 0.61 (95% confidence interval, 0.53-0.71)). This reduced risk was observed both in patients with vascular disease and in patients with risk factors. The associations were similar across the different manifestations of vascular disease., Conclusions: Higher levels of leisure time physical activity were associated with reduced risk of vascular events and all-cause mortality in patients with CAD and other manifestations of vascular disease, suggesting that physical exercise programs should also be investigated in these other manifestations.

Background: For parents at high risk for cardiovascular events, presence of cardiovascular disease or risk factors in their offspring may be an indicator of their genetic load or exposure to (unknown) risk factors and might be related to the development of new or recurrent vascular events., Methods: In 4,267 patients with vascular disease, hypertension, diabetes, or hypercholesterolemia enrolled in the SMART cohort, the presence of cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking, or overweight) and cardiovascular disease (coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm) was assessed in their 10,564 children. The relation between presence of cardiovascular disease or cardiovascular risk factors in their offspring and new or recurrent vascular events was determined by Cox proportional hazard analyses., Results: Of the patients, 506 (12%) had offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes. Smoking in offspring was present in 1,972 patients (46%), and overweight in 845 patients (20%). During a median follow-up of 7.0 years (interquartile range 3.7-10.4), the composite outcome of myocardial infarction (MI), stroke, or vascular mortality occurred in 251 patients. Patients with offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes had an increased risk of vascular mortality (hazard ratio [HR] 2.9, 95% CI 1.2-7.1), MI (HR 1.6, 95% CI 1.1-2.5), and the composite outcome (HR 1.5, 95% CI 1.1-2.2). Diabetes in offspring was related to an increased risk of the composite outcome (HR 2.7, 95% CI 1.5-5.0), MI (HR 3.3, 95% CI 1.7-6.6), and vascular mortality (HR 3.4, 95% CI 0.8-14.8). Smoking and overweight in offspring were not related to increased vascular risk in parents., Conclusions: Presence of cardiovascular disease, hypertension, hypercholesterolemia, and diabetes in offspring, with diabetes mellitus being the most contributing cardiovascular risk factor, is related to an increased risk of developing new or subsequent vascular events in patients already at high vascular risk., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Genetic inhibition of Cholesteryl Ester Transfer Protein (CETP) might be associated with insulin resistance and incident type 2 diabetes mellitus (T2DM). This study investigated the relation between a genetic variant in the CETP gene and measures of insulin resistance and incident T2DM in patients with manifest cardiovascular disease (CVD). Furthermore the effect on risk of recurrent cardiovascular events was investigated., Methods: SMART is a prospective cohort study performed in 5601 patients with clinically manifest CVD. We selected a variant (rs3764261) associated with reduced CETP activity and increased levels of HDL cholesterol (HDL-C). Patients were divided in three groups: 2640 wild type patients (GG), 2420 heterozygotes for rs3764261 (GT) and 541 homozygotes for rs3764261 (TT). Regression analyses were performed using an additive model., Results: The study population consisted of 4656 patients without T2DM and 945 patients with T2DM at baseline. Presence of rs3764261 was associated with increased HDL-C in patients without T2DM (β 0.106, 95%CI 0.083-0.128) and with T2DM (β 0.043, 95%CI 0.007-0.078). During a median follow up of 7.2 years (IQR 4.7-10.2) 427 incident T2DM occurred. Presence of rs3764261 was not related to incident T2DM (HR 0.96, 95%CI 0.83-1.11) in patients without T2DM at baseline. Furthermore, presence of rs3764261 was not related to insulin resistance (glucose, insulin, HOMA-IR, HbA1c) or recurrent CVD (HR 0.92, 95%CI 0.84-1.02)., Conclusion: Presence of CETP SNP rs3764261 is not associated with insulin resistance and incident T2DM in patients with clinically manifest vascular disease. Furthermore, no effect of rs3764261 on the risk of recurrent CVD was observed., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Depressive symptoms and cognitive impairment often co-occur, but their interactive relationship is complex and the direction of causation is still a topic of research. We examined the influence of cognitive performance on the course of depressive symptoms during 7 years of follow-up in patients with vascular disease., Method: Within the SMART-MR study, 736 patients (mean age 62 ± 10 years) had neuropsychological assessment on four cognitive domains at baseline [memory (MEM), working memory (WMEM), executive functioning (EXEC), and information processing speed (SPEED)]. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline and every 6 months during 7 years of follow-up. Generalized Estimating Equation (GEE) models were used to assess the association between cognitive performance with depressive symptoms at multiple time points during follow-up. Interaction terms between the respective cognitive domains and time was included to examine if the course of depressive symptoms differed according to baseline cognitive performance., Results: The GEE analyses showed no significant interactions between the respective cognitive domains and time indicating no different course of depressive symptoms according to baseline cognitive performance. Lower MEM, EXEC or SPEED, but not WMEM performance, was significantly associated with more depressive symptoms during follow-up per z score decrease: MEM [B = 0.70, 95% confidence interval (CI) 0.35-1.05]; EXEC (B = 0.88, 95% CI 0.41-1.36), and SPEED (B = 0.57, 95% CI 0.21-0.92)., Conclusions: Poorer cognitive performance on the domains MEM, EXEC and SPEED, but not WMEM, was associated with higher levels of depressive symptoms over 7 years of follow-up, but not with a different course of depressive symptoms over time.

Several trials and cohort studies have shown an increased incidence of type 2 diabetes mellitus (T2DM) in patients using statins. Whether this only applies to patients at already high risk for the development of T2DM or for all patients is still a matter of debate. In the present prospective cohort study of 4,645 patients with established vascular disease without DM at baseline, 3,057 patients used statins at baseline, of whom 1,608 used intensive statin therapy, defined as statin therapy theoretically lowering low-density lipoprotein cholesterol with ≥40%. Cox proportional hazards models were used to estimate the risk of incident T2DM with (intensive) statin therapy. Statin therapy was associated with increased risk of incident T2DM (hazard ratio 1.63; 95% confidence interval 1.15 to 2.32) when adjusted for age, gender, body mass index, plasma high-density lipoprotein cholesterol, and plasma triglyceride levels. Intensive statin therapy tended to be related to a higher risk of T2DM compared with moderate statin therapy (hazard ratio 1.22; 95% confidence interval 0.92 to 1.61, adjusted for age, gender, body mass index, plasma high-density lipoprotein cholesterol, and plasma triglyceride levels). The increase in risk was regardless of the number of metabolic syndrome characteristics or insulin resistance but was particularly present in patients with low baseline glucose levels (<5.6 mmol/L; p for interaction 2.9 × 10(-7)). In conclusion, statin use increases the risk of incident T2DM in patients with clinically manifest vascular disease. The increase in risk was independent of the number of metabolic syndrome criteria and was even more pronounced in patients with low baseline glucose levels., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Apolipoprotein E (APOE) genotypes are associated with different plasma lipid levels. People with the APO ɛ2 genotype can develop a disorder called dysbetalipoproteinemia (DBL). A possible predisposing factor for DBL is adiposity. We evaluated whether and to what extent the APOE genotype modifies the relation between adiposity and lipids in patients with manifest arterial disease and we looked at possible determinants of DBL in ɛ2 homo- and heterozygote patients., Methods: This prospective cohort study was performed in 5450 patients with manifest arterial disease from the Secondary Manifestations of ARTerial disease (SMART) study. The APOE genotype was measured in all patients and revealed 58 ɛ2 homozygotes, 663 ɛ2 heterozygotes, 3181 ɛ3 homozygotes and 1548 ɛ4 carriers. The main dependent variable was non-high-density lipoprotein cholesterol (non-HDL-c). The relation between adiposity (including body mass index (BMI), waist circumference (waist), visceral adipose tissue (VAT) and metabolic syndrome (MetS)) and lipids was evaluated with linear regression analyses. Determinants of DBL were evaluated using logistic regression., Results: There was significant effect modification by the APOE genotype on the relation between non-HDL-c and BMI, waist, VAT and MetS. There was an association between BMI and non-HDL-c in ɛ2 homozygotes (β 0.173, 95% confidence interval (CI) 0.031-0.314, P=0.018) and ɛ4 carriers (β 0.033, 95% CI 0.020-0.046, P<0.001). In all genotypes, there was an effect of waist, VAT and MetS on non-HDL-c, but these effects were most distinct in ɛ2 homozygotes (waist β 0.063, 95% CI 0.015-0.110, P=0.011; VAT β 0.580, 95% CI 0.270-0.889, P=0.001; MetS β 1.760, 95% CI 0.668-2.852, P=0.002). Determinants of DBL in ɛ2 homo- and heterozygotes were VAT and MetS., Conclusion: The APOE genotype modifies the relation between adiposity and plasma lipid levels in patients with vascular disease. The relation between adiposity and lipids is present in all patients, but it is most distinct in ɛ2 homozygote patients. Abdominal fat and MetS are determinants of DBL.

Background: Previous studies suggest that elevated resting heart rate (RHR) is related to an increased risk of cancer mortality. The aim of this study was to evaluate the relation between RHR and cancer incidence and mortality in patients with vascular disease., Methods: Patients with manifest vascular disease (n=6007) were prospectively followed-up for cancer incidence and mortality. At baseline, RHR was obtained from an electrocardiogram. The relation between RHR and cancer incidence, cancer mortality and total mortality was assessed using competing risks models., Results: During a median follow-up of 6.0 years (interquartile range: 3.1-9.3) 491 patients (8%) were diagnosed with cancer and 907 (15%) patients died, 248 (27%) died from cancer. After adjustment for potential confounders, the hazard ratio (HR) for incident cancer per 10 beats/min increase in RHR was 1.00 (95% confidence interval [CI]: 0.93-1.07). There was a trend toward an increased risk of colorectal cancer in patients with higher RHR (HR 1.15, 95% CI 0.97-1.36). The risk of all-cause mortality was increased in patients in the highest quartile of RHR compared to the lowest quartile (HR 1.86, 95% CI 1.53-2.27), but no effect of RHR on cancer mortality was observed (HR 1.01, 95% CI 0.70-1.46)., Conclusions: In patients with manifest vascular disease, elevated RHR was related to a higher risk of premature all-cause mortality, but this was not due to increased cancer mortality. RHR was not related to risk of overall cancer incidence, although a relation between elevated RHR and incident colorectal cancer risk could not be ruled out., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients., Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events., Results: The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13)., Conclusion: The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients.

Background: Several single-nucleotide polymorphisms (SNPs) are associated with both plasma low-density lipoprotein cholesterol (LDL-c) level and coronary artery disease in the general population. It is unclear whether these associations also apply to patients with vascular disease and whether the associations are independent of lipid-lowering therapy., Design: Single-nucleotide polymorphisms associated with plasma LDL-c and vascular risk in the general population (rs11206510 (PCSK9), rs1122608 (LDLR), rs579459 (ABO) and rs599839 (SORT1)) were genotyped in a prospective cohort study of 5482 patients with vascular disease. We determined the association between LDL-c-associated alleles and plasma LDL-c levels and the risk of new vascular events., Results: All tested SNPs were associated with LDL-c plasma levels with a magnitude between +0·06 (95% CI 0·02-0·10) mM and +0·14 (95% CI 0·09-0·18) mM per LDL-c-increasing allele. The associations were independent of the use of lipid-lowering medication, except for rs579459, for which the association was not present in patients using lipid-lowering medication. In patients with 7-8 risk alleles for these SNPs, 59% of the patients treated with lipid-lowering medication did not reach the LDL-c target of <2·5 mM compared with 45% in patients with 3 or fewer risk alleles. LDL-c-increasing alleles were not associated with increased risk of vascular events in patients not using lipid-lowering medication (HRs: 1·01; 95% CI: 0·93-1·09). In patients using lipid-lowering medication, the risk of myocardial infarction increased with 14% (HRs: 1·14; 95% CI: 1·01-1·28) per allele., Conclusions: In patients with established vascular disease, the studied SNPs increase LDL-c plasma levels. LDL-c-increasing alleles may be associated with increased risk of myocardial infarction in patients treated with lipid-lowering medication, but not in patients not treated with lipid-lowering medication., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objectives: Extracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of four previously identified EV proteins (cystatin C, serpin G1, serpin F2 and CD14) are associated with cerebral white matter lesions (WMLs) and brain atrophy., Design: Cohort study; cross-sectional and prospective., Setting: Single centre, secondary and tertiary setting., Participants: 1309 patients with manifest vascular disease from the Second Manifestations of ARTerial disease-MR (SMART-MR) study, of which 994 had successful brain MRI and EV protein level measurements., Outcomes: WML and brain parenchymal fraction (BPF), as parameter for brain atrophy, at baseline and follow-up., Statistical Methods: The relationship between EV protein levels and WML volume (expressed as log transformed percentage of intracranial volume) and BPF (expressed percentage of intracranial volume) on 1.5 T brain MRI was assessed with multivariable linear regression modelling. Subsequently, the relationship between baseline EV protein levels and progression of atrophy and WML was analysed in 534 patients, in whom a follow-up MRI was obtained after 4 years., Results: Higher EV-cystatin C and EV-CD14 were significantly associated with larger WML volume (linear regression coefficient (95% CI) 0.10 log %/SD (0.04 to 0.17) and 0.14 log %/SD (0.07 to 0.20), respectively. Higher EV-CD14 was associated with more brain atrophy (-0.14%/SD; -0.27 to -0.01). Baseline EV-CD14 was significantly associated with increase of WMLs (0.11 log %/SD (0.04 to 0.18)). No relationship with EV-serpins was observed at baseline or at follow-up., Conclusions: EV proteins cystatin C and CD14 are related to cerebral WMLs and the progression of brain atrophy in patients with manifest vascular disease, potentially identifying EVs in the aetiology of structural brain changes.

Background and Objectives: Microvesicles (MVs) are small membrane vesicles that are involved in atherotrombotic processes. In the present study, we evaluated the risk of MV protein levels on the occurrence of new vascular events in patients with clinically manifest vascular disease., Methods: In this cohort study 1060 patients were prospectively followed for the occurrence of a new vascular event or death (median follow up 6.4 years, interquartile range 5.2-7.3 years). MVs were isolated from plasma and MV protein levels of Cystatin C, Serpin G1, Serpin F2 and CD14 were measured. Multivariable Cox proportional hazards models were used to estimate the risk for new vascular events, vascular mortality and all-cause mortality. During follow up 136 vascular events occurred, 65 vascular mortality and 114 all-cause mortality., Results: An increase in 1 standard deviation (SD) of Cystatin C MV level was related to an increased risk for myocardial infarction (HR 1.49; 95%CI 1.20-1.86), vascular mortality (HR 1.48; 95%CI 1.17-1.86), vascular events (HR 1.27; 1.07-1.52) and all-cause mortality (HR 1.41; 95%CI 1.18-1.69). Serpin F2 MV levels were related to an increased risk for myocardial infarction (HR 1.22; 95%CI 1.00-1.51), vascular mortality (HR 1.25; 95%CI 1.00-1.56), and all-cause mortality (HR 1.22; 95% CI 1.03-1.45). CD14 MV levels were related to an increased risk for myocardial infarction (HR 1.55; 95%CI 1.27-1.91), vascular mortality (HR 1.37; 95%CI 1.10-1.70), vascular events (HR 1.32; 95%CI 1.12-1.55), all-cause mortality (HR 1.36; 95%CI 1.15-1.62) and occurrence of ischemic stroke (HR 1.32; 95%CI 1.00-1.74)., Conclusions: Cystatin C, Serpin F2 and CD14 MV levels are related to an elevated risk for future vascular events and mortality in patients with clinically manifest vascular disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim: Based on guidelines, patients with established cardiovascular disease are likely to already receive a combination of aspirin, a statin, and blood pressure (BP)-lowering agents. Combining these pharmacological agents into a cardiovascular polypill could be considered in these patients to reduce prescription gaps and non-adherence. We aimed to assess the prevalence of the combined use of aspirin, statin, and BP-lowering agents in patients with established cardiovascular diseases or type 2 diabetes mellitus (DM2) in the period 1996-2009., Methods: In total, 5702 patients with coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial occlusive disease (PAOD), abdominal aortic aneurysm (AAA) or, DM2 were included in the period 1996-2009., Results: The overall use of combination therapy with aspirin, statin, and ≥ 1 BP-lowering agent increased substantially from 9% in 1996 to 66% in 2009 and ≥ 2 BP-lowering agents increased from 1% to 47%. In 2009, combination therapy with ≥ 1 BP-lowering agent was used by 83% of those with CAD, 48% of those with CVD, 43% of those with PAOD, 36% of the patients with AAA, and 19% of the patients with DM2. In most patient groups, obesity, metabolic syndrome, hypertension concomitant CAD, CVD, or DM2 were related to the use of combination therapy in models adjusted for age and gender., Conclusion: A high proportion of patients with established cardiovascular diseases already uses a combination of pharmacological agents. Introduction of a polypill in high-risk patients might be feasible to reduce prescription gaps and increase adherence to indicated therapy.

Introduction: Systemic low-grade inflammation, as measured by high-sensitive C-reactive protein (hsCRP), may contribute to the risk of type 2 diabetes in patients with manifest arterial disease., Methods: Cohort study in 4072 patients with manifest arterial disease without diabetes. The relation between quartiles of hsCRP and type 2 diabetes was assessed with Cox regression analyses, taking age, smoking and blood pressure-lowering medication and lipid-lowering medication into account. Insulin resistance was estimated with homeostasis model of insulin resistance (HOMA-IR). In exploratory models, adjustments were performed for body mass index (BMI) and visceral and subcutaneous adipose tissue thickness., Results: During a median follow-up of 5·0 (IQR 2·5-8·2) years, 288 subjects developed diabetes. High hsCRP was independently associated with incident diabetes (Q4 vs. Q1 males: HR 1·62; 95% CI 1·06-2·48; females: HR 3·12; 95% CI 1·57-6·21). HOMA-IR at baseline is related to hsCRP plasma levels (Q4 vs. Q1: males: β 0·27; 95% CI 0·19-0·36; females: β 0·35; 95% CI 0·22-0·48). The risk of diabetes associated with hsCRP was abolished in males (Q4 vs. 1 HR 1·23; 95% CI 0·80-1·88) and attenuated in females (Q4 vs. 1 HR 2·32; 95% CI 1·14-4·75) after adding BMI to the model, but not modified by statin use (P for interaction: 0·61)., Conclusions: Patients with manifest arterial disease with high hsCRP plasma levels are at increased risk to develop type 2 diabetes and are more insulin resistant as compared to those with low hsCRP levels. This increase in risk is more pronounced in females than in males and is not modified by statin use., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Resting heart rate (RHR) reflects sympathetic nerve activity and is independently related to the occurrence of cardiovascular events and death in healthy subjects, patients with coronary artery disease (CAD) and patients with cardiovascular risk factors. We investigated and compared the risk of RHR on the occurrence of cardiovascular events and death in patients with CAD, cerebrovascular disease (CVD), peripheral arterial disease (PAD) or abdominal aortic aneurysm (AAA)., Methods: Data were used from a prospective cohort study of 4272 patients with manifest vascular disease: CAD (n=2244), CVD (n=930), PAD (n=823) or AAA (n=275). RHR was obtained at baseline from an electrocardiogram. The median follow-up time was 4.4 (interquartile range 2.1-7.4) years. The relation between RHR and the occurrence of cardiovascular events and death was estimated by Cox proportional hazard analyses., Results: Each increase in RHR of 10 beats/min was related to an increased risk for all-cause mortality (hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.07-1.21) and vascular mortality (HR 1.15; 95% CI 1.06-1.25), but not for myocardial infarction (HR 1.03; 95% CI 0.94-1.14) or ischemic stroke (HR 1.05; 95% CI 0.92-1.20). The relation between an increased RHR and increased risk for all-cause mortality was present irrespective of beta-blocker use and irrespective of the location of vascular disease: CAD (HR 1.23; 95% CI 1.05-1.44), CVD (HR 1.18; 95% CI 1.05-1.33) and PAD/AAA (HR 1.10; 95% CI 1.01-1.20)., Conclusions: Elevated RHR is associated with increased risk for mortality but not for myocardial infarction or stroke in patients with manifest vascular diseases irrespective of location of vascular disease., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Importance: Studies have shown that both high and low blood pressure (BP) may play a role in the etiology of brain atrophy. High BP in midlife has been associated with more brain atrophy later in life, whereas studies in older populations have shown a relation between low BP and more brain atrophy. Yet, prospective evidence is limited, and the relation remains unclear in patients with manifest arterial disease., Objective: To examine the associations of baseline BP and change in BP over time with progression of brain atrophy., Design: The Secondary Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) Study is a prospective cohort study with baseline measurements in 2001-2005 and follow-up measurements in 2006-2009. The mean follow-up time was 3.9 years., Setting: University Medical Center Utrecht, the Netherlands., Participants: A total of 663 patients (mean [SD] age, 57 [9] years; 81% male) with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm were included., Main Outcomes and Measures: Using automated segmentation at baseline and follow-up, change in brain parenchymal fraction, cortical gray matter fraction, and ventricular fraction (%ICV) were quantified as indicators of progression of global, cortical, and subcortical brain atrophy., Results: Multivariable adjusted regression analysis showed that patients with lower baseline diastolic BP (DBP) or mean arterial pressure had more progression of subcortical atrophy. The mean differences in the change in ventricular fraction between low and high DBP was 0.07% (95% CI, 0.01-0.14) and between low and high mean arterial pressure was 0.05% (95% CI, 0.00-0.10). Furthermore, in patients with higher baseline BP (DBP, mean arterial pressure, or systolic BP), those with declining BP levels over time had less progression of subcortical atrophy compared with those with rising BP levels., Conclusions and Relevance: In patients with manifest arterial disease, low baseline DBP was associated with more progression of subcortical atrophy, irrespective of the BP course during follow-up. Furthermore, in patients with higher baseline BP, declining BP levels over time were associated with less progression of subcortical atrophy. This could imply that BP lowering is beneficial in patients with higher BP levels, but caution should be taken with further BP lowering in patients who already have a low DBP.

Background: Plasma triglyceride (TG) levels are known to confer an increased risk of vascular disease in healthy populations, but data in high-risk patients are scarce. In this study we evaluated the risk on recurrent vascular events conferred by increased plasma TG levels in patients with various clinical manifestations of vascular disease., Methods: Prospective cohort study of 5731 patients with clinically manifest vascular disease., Results: First new vascular events (myocardial infarction, ischemic stroke, vascular death) occurred in 782 subjects during a median follow-up of 4.9 years (interquartile range 2.5-8.1 years). Patients in the highest plasma TG quintile (>2.24 mmol/L) had a higher risk for recurrent vascular events (HR 1.45; 95%CI 1.13-1.86) compared with the lowest plasma TG quintile (<0.97 mmol/L) after adjustments for age, gender, body mass index, smoking, lipid-lowering medication and low-density lipoprotein-cholesterol. The increased risk associated with increasing plasma TG levels was irrespective of the presence of type 2 diabetes (T2DM), but only present in patients without the metabolic syndrome. Furthermore, the increased risk was particularly present in patients with coronary artery disease (CAD) (HR 1.45; 95%CI 1.02-2.08) and was not modified by other lipid levels (p-value for interaction >0.05). Plasma TG still contributed to vascular risk when other lipid levels were at target level., Conclusions: Higher plasma TG levels are associated with increased risk for recurrent vascular events, in particular in CAD patients. This increased risk is independent of the presence of T2DM and the use of lipid-lowering medication and is not modified by other lipid levels., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with vascular disease may be at increased risk of cancer because of shared risk factors and common pathogenesis., Methods: Patients with vascular disease (n = 6,172) were prospectively followed for cancer incidence. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence of the study population with that of the general population. Multivariable-adjusted hazard ratio's (HRs) of cancer were estimated for smoking status, pack-years, body mass index, waist circumference and visceral adipose tissue (VAT), and metabolic syndrome (MetS)., Results: During a median follow-up of 5.5 years, 563 patients were diagnosed with cancer. Patients with vascular disease were at increased risk of cancer [SIR = 1.19; 95% confidence interval (CI), 1.10-1.29]. Specifically, risk of lung cancer (SIR = 1.56; 95% CI, 1.31-1.83), as well as bladder cancer (SIR = 1.60; 95% CI, 1.11-2.24) and cancer of the lip, oral cavity, or pharynx in men (SIR = 1.51; 95% CI, 0.89-2.39), and colorectal (SIR = 1.71; 95% CI, 1.11-2.53) and kidney cancer (SIR = 2.92; 95% CI, 1.05-6.38) in women was increased. A relation between smoking and cancer risk was observed (HR for current smokers = 1.37; 95% CI, 1.05-1.73), whereas an increase in VAT was associated with higher breast cancer risk in women (HR = 1.42; 95% CI, 1.03-1.96). No relation between MetS and cancer risk was found., Conclusions: Patients with vascular disease have a 19% higher cancer risk compared to the general population. Smoking increased cancer risk and abdominal obesity is a risk factor for breast cancer in female patients with vascular disease., Impact: These results call for awareness of the increased cancer risk in patients with vascular disease among physicians and underline the necessity of lifestyle improvement not only for reducing cardiovascular risk.

Background and Purpose: Because best medical treatment is improving, the risk of stroke in asymptomatic carotid artery stenosis (ACAS) may decline. We evaluated the risk of ischemic stroke and stratified it according to stroke subtype in patients with ACAS during long-term follow-up., Methods: In total, 4319 consecutive patients in the Second Manifestations of Arterial disease study with clinically manifest arterial disease or specific risk factors, but without a history of cerebrovascular disease, were included. Degree of stenosis was evaluated with duplex ultrasound scanning. Strokes during follow-up were classified according to subtype. Cox-proportional hazard-regression models were used to evaluate the relationship between ACAS and future stroke., Results: We identified 293 (6.8%) patients with ACAS 50% to 99%, of whom 193 had 70% to 99% stenosis. In these subgroups, mean follow-up was 6.2 and 6.0 years, respectively. In total, 94 ischemic strokes occurred, of which 8 in ACAS 50% to 99% patients. The any territory annual ischemic stroke risk was 0.4% in 50% to 99% ACAS and 0.5% per year for 70% to 99% ACAS patients. The risk of ischemic stroke was not significantly increased in patients with ACAS 70% to 99% (hazard ratio, 1.5; 95% confidence interval, 0.7-3.5). Patients with ACAS 50% to 99% and ACAS 70% to 99% tended to have nonsignificantly more large vessel disease strokes (hazard ratio, 1.5; 95% confidence interval, 0.5-4.2 and hazard ratio, 1.7; 95% confidence interval, 0.5-5.6)., Conclusions: Patients with clinically manifest arterial disease or type 2 diabetes mellitus have a low risk of developing ischemic stroke, irrespective of its subtype and independent of the degree of ACAS stenosis.

Objective: Presence of hypertensive target organ damage is related to increased vascular risk and mortality. Whether combined presence of hypertensive target organ damage confers higher vascular risk compared to single presence is unknown. This study evaluates the separate and combined effects of impaired renal function [estimated glomerular filtration rate (eGFR) ≤60 ml/min per 1.73 m], albuminuria (albumin/creatinine-ratio men ≥2.5 mg/mmol, women ≥3.5 mg/mmol) and left-ventricular hypertrophy (LVH) (Sokolow-Lyon and/or Cornell-voltage criterion) on the occurrence of vascular events and mortality in patients with vascular disease (coronary artery disease, cerebrovascular disease, and peripheral arterial disease)., Methods and Results: A cohort of patients with vascular diseases (n = 4319) was followed (median 4.4 years) for the occurrence of vascular events (stroke, myocardial infarction, vascular death) and mortality. LVH was present in 11%, impaired renal function in 15%, and albuminuria in 18%. Presence of at least two hypertensive target organ damage was prevalent in 8%. The risk for vascular events was hazard ratio 1.5 [95% confidence interval (CI) 1.2-1.9] for presence of one hypertensive target organ damage and hazard ratio 3.8 (95% CI 2.3-6.3) for three manifestations of hypertensive target organ damage (adjusted for age, sex). For mortality this was hazard ratio 1.4 (95% CI 1.1-1.7) and hazard ratio 3.2 (95% CI 1.9-5.2). Hazard ratios for single presence of different types of organ damage were comparable and independent of the presence of hypertension., Conclusions: Impaired renal function, albuminuria, and LVH are prevalent in patients with vascular disease and confer independent and additive risk for vascular events and mortality. Measurement of hypertensive target organ damage in patients with vascular disease identifies patients at very high risk and may have treatment implications.

Objectives: To quantify the relation between adiposity and blood pressure (BP) level in patients with symptomatic vascular disease and, thereby, assess whether the obesity paradox can be explained by a causal mechanism involving BP., Methods: BP and markers of adiposity (i.e. weight, body mass index, waist circumference, waist-to-hip ratio, subcutaneous adipose tissue, and visceral adipose tissue) were recorded in 4556 men and women with symptomatic vascular disease enrolled in the Secondary Manifestations of Arterial Disease Study. Additionally, 185 patients underwent repeated measurements after 3.7 years follow-up., Results: Each 5 kg/m(2) body mass index was associated with +3.8 mmHg (95% confidence interval (CI) 3.0-4.6) SBP difference and +2.3 mmHg (95% CI 1.9-2.8 mmHg) DBP difference in both men and women. Measures of centralized adiposity compared with BMI were equally related with BP. In contrast, subcutaneous adipose tissue was only weakly related with DBP and not related with SBP and pulse pressure. Various methods of adjustment for BP-lowering medication use led to consistent results. Furthermore, 5 kg/m(2) body mass index change during follow-up was associated with +8.1/5.1 mmHg BP change., Conclusion: The relation between general and abdominal adiposity and hypertension persists after onset of symptomatic arterial disease both in men and women. This shows that the obesity paradox cannot be explained by a causal mechanism involving BP and, therefore, supports weight control for reducing BP in secondary prevention of cardiovascular events.

Higher body weight is associated with an increased prevalence of vascular risk factors. Obesity leads to hypertension by various mechanisms, often referred to as obesity-related hypertension. Aim of the present study was to evaluate the prevalence and the vascular risk of the combination of obesity and hypertension in patients with vascular diseases. A cohort of patients with various clinical manifest vascular diseases (n = 4,868) was screened for vascular risk factors and followed (median follow-up 4.2 years) for the occurrence of vascular events (stroke, myocardial infarction, and vascular death). The prevalence of obesity was 18% (95% confidence interval (CI) 17-19%) and the prevalence of hypertension was 83% (95% CI 82-84%). The prevalence of the combination of obesity and hypertension was 16% (95% CI 15-17%). Patients with high blood pressure (BP) combined with a high weight (highest tertile systolic BP (SBP) in the highest tertile BMI) were not at higher risk for new vascular events (hazard ratios (HR) 1.29; 95% CI 0.89-1.88) or mortality (HR 1.18; 95% CI 0.81-1.73) compared to patients without high BP and high weight (patients in the lowest tertile of SBP in the lowest tertile of BMI). Patients with only high weight did not have an elevated risk either for vascular events (HR 1.34; 95% CI 0.91-1.98) or mortality (HR 1.22; 95% CI 0.81-1.83) compared to patients without high BP and high weight. The prevalence of the combination of hypertension and obesity is low in patients with vascular diseases and does not confer a higher risk for recurrent vascular diseases and mortality than each risk factor alone.

Aims: To investigate whether levels of thyroid-stimulating hormone (TSH) within the normal range are associated with an increased risk of new vascular events and mortality in patients with clinical manifest vascular diseases and whether this relation is influenced by adiposity., Methods and Results: Prospective cohort study in 2443 patients (1790 men and 653 women) with clinical manifest vascular disease and TSH levels in the normal range. Median follow up was 2.7 (interquartile range 1.4-3.9) years. Clinical endpoints of interest were: myocardial infarction, stroke, vascular death, and all-cause mortality. In patients with manifest vascular disease, the prevalence of (subclinical) hypothyroidism was 5.7%, while 3.6% had (subclinical) hyperthyroidism. An increase in 1 unit of TSH was associated with a 33% higher risk (HR 1.33; 95% CI 1.03-1.73) for the occurrence of myocardial infarction, adjusted for age, gender, renal function, and smoking. In patients with a body mass index (BMI) below the median of 26.7 kg/m(2) the HR per unit TSH for myocardial infarction was 1.55 (95% CI 1.08-2.21) compared to 1.18 (95% CI 0.81-1.71) in patients with a BMI ≥26.7 kg/m(2). Visceral adipose tissue thickness below the median (≤8.8 cm) was associated with higher HR per unit TSH for myocardial infarction (HR 1.69; 95% CI 1.21-2.35) compared to visceral adipose tissue thickness >8.9 cm (HR 1.00; 95% CI 0.66-1.49). There was no relation between TSH and risk of stroke, vascular death, the combined endpoint, or all-cause mortality., Conclusion: Higher TSH levels within the normal range are associated with an increased risk of myocardial infarction, in patients with clinical manifest vascular disease. This relation is most prominent in patients without visceral obesity.

Objective: Sympathetic nerve activation is causally related to insulin resistance as both a cause and a consequence. Resting heart rate (RHR) reflects sympathetic nerve activity. We investigated the effect of RHR on the incidence of type 2 diabetes mellitus (T2DM) in patients with clinically manifest vascular diseases., Design: Data were used from the second manifestations of arterial disease (SMART) study: a prospective cohort study of patients with clinically manifest vascular diseases (n=3646)., Methods: RHR was obtained using an electrocardiogram. Patients were followed up for incident type 2 diabetes (n=289) during a median period of 5.5 (interquartile range 3.2-8.4) years. The relation between RHR and incident T2DM was estimated by Cox proportional hazard analysis. As age was an effect modifier (P=0.048), analyses were stratified for age., Results: Patients in quartile 4 (Q4) of RHR had a 65% increased risk of T2DM compared with those in Q1 (reference; hazard ratios (HR), 1.65; 95% confidence interval (95% CI), 1.15-2.36) adjusted for age, gender, smoking, estimated glomerular filtration rate, systolic blood pressure, location of vascular disease, and antihypertensive medication. Every 10 beats per minute (bpm) increase in RHR increased the risk for T2DM with 10% (HR, 1.10; 95% CI, 1.00-1.21) in the total population. This risk was particularly high in subjects aged 55-63 years (per 10 bpm: HR, 1.22; 95% CI, 1.04-1.43) and was independent of the location of vascular disease and beta-blocker use., Conclusions: Increased RHR, an indicator of sympathetic nerve activity, is associated with an increased risk for T2DM in patients with manifest vascular diseases, particularly in middle-aged patients.

Objective: This study investigated the relation between alcohol consumption and specific vascular events and mortality in a high risk population of patients with clinical manifestations of vascular disease and diabetes., Methods: Patients with clinically manifest vascular disease or diabetes (n=5447) from the SMART study were followed for cardiovascular events and mortality. Alcohol consumption was assessed with a baseline questionnaire and analysed in relation with coronary heart disease (CHD), amputations, stroke, and all-cause and vascular death., Results: After a follow up of 4.7 years, we documented 363 cases of CHD, 187 cases of stroke, 79 amputations and 641 cases of all-cause death, of which 382 were vascular. In multivariate-adjusted models, alcohol consumption was inversely associated with CHD (p(linear trend)=0.007) and stroke (p(linear trend)=0.051) with respective hazard ratios of 0.39 (95%CI: 0.20-0.76) and 0.67 (0.31-1.46) for consuming 10-20 drinks/week compared with abstainers. We observed significant U-shaped associations between alcohol consumption and amputations (p(quadratic trend)=0.001), all-cause death (p(quadratic trend)=0.001) and vascular death (p(quadratic trend)=0.013). Hazard ratios for consuming 10-20 drinks/week were 0.29 (0.07-1.30) for amputations, 0.40 (0.24-0.69) for all-cause death and 0.34 (0.16-0.71) for vascular death compared with abstainers. Similar associations were observed for red wine consumption only., Conclusion: Moderate alcohol consumption (1-2 drinks/day) is not only associated with a reduced risk of vascular and all-cause death in a high risk patients with clinical manifestations of vascular disease, but also with reduced risks of non-fatal events like CHD, stroke and possibly amputations., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Self-management can improve health behaviors and influence reduction of vascular risk. We developed a 1-year self-management intervention and investigated its effect on vascular risk factors and quality of life in patients with different vascular diseases., Design and Methods: This observational cohort study involved 223 patients (self-management group, n=125; usual care group n=98) with at least two modifiable vascular risk factors., Results: Patients in the self-management group achieved treatment goals for LDL-cholesterol (difference 13%; 95%CI 1-26) and HDL-cholesterol (difference 9% 95%CI 0-19) significantly more often than did patients in the usual care group. Mean systolic blood pressure decreased significantly by 5mm Hg (95%CI -9 to 0) in the self-management group and mean BMI increased significantly by 0.4 kg/m(2) (95%CI -0.8 to -0.1) in the usual care group. No significant differences were seen in waist circumference, smoking, or triglycerides. General health (RAND36) improved more in the self-management group (by 8 points 95%CI 3-12) than in the usual care group., Conclusion: After 1 year, the self-management intervention was more effective than usual care on several important vascular risk factors in patients with vascular diseases., Practice Implications: This self-management intervention used in a hospital population may be applicable in different care settings., (Copyright (c) 2009 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate the effect of leisure-time physical activity on the incidence of type 2 diabetes (T2DM) in patients with manifest arterial disease, or poorly controlled risk factors., Methods: We examined 3940 patients with manifest arterial disease, hypertension or hyperlipidemia, aged 55.2+/-12.2 years. Leisure-time physical activity was measured by a questionnaire and metabolic equivalent (MET) hours per week (h/wk) were calculated. Incident T2DM was evaluated by a specific diabetes questionnaire., Results: Most patients (65%) were physically inactive (0METh/wk), 12% were insufficiently physically active (0-10.5METh/wk) and 23% were sufficiently physically active (>or=10.5METh/wk). During a mean follow-up of 4.7 years, 194 (5%) incident cases of T2DM occurred. Sufficiently physically active patients had a lower incidence of diabetes (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.37-0.83). Patients who were physically active and not-obese (BMI<30kg/m(2)) were at the lowest risk for developing T2DM (HR 0.18, 95% CI 0.12-0.28) compared with patients who were physically inactive and obese., Conclusions: Leisure-time physical activity is associated with a decreased risk of T2DM in patients with manifest arterial disease, or poorly controlled risk factors. The combination of physical activity and non-obesity is associated with an even lower risk of the development of type 2 diabetes than the sum of their independent, protective effect.

Background: Cerebral atrophy on brain magnetic resonance imaging (MRI) has been associated with vascular risk factors including hypertension. Progression of cerebral atrophy and its risk factors have not been studied in vascular disease patients. This study aimed to assess the progression of cerebral atrophy and to evaluate possible associations with blood pressure (BP) in patients with pre-existing vascular disease., Methods: A total of 331 patients with manifest vascular disease from the Second Manifestations of ARTerial Disease (SMART) Study underwent baseline and follow-up MRI scanning (mean follow-up 4.1 +/- 0.3 years). The annual change in brain and ventricular volume was calculated with an automated quantitative volumetric method. Associations between BP and change in brain and ventricular volumes and between BP and the occurrence of lacunar infarcts were analyzed., Results: At baseline mean age was 58 +/- 9 years and mean BP was 138/80 mm Hg. Mean annual decrease in brain tissue volume was 6.5 +/- 3.8 ml and mean annual increase in ventricular volume was 1.0 +/- 1.0 ml. There was no association observed between BP and annual change in brain or ventricular volume, but a clear association was found between BP and incident lacunar infarcts (odds ratio 1.57; 1.11-2.22 per s.d. increase in systolic BP (SBP))., Conclusions: The magnitude of changes in brain tissue and ventricular volume in patients with vascular disease was comparable to the physiological changes described in normal people at a much higher age. Progression of cerebral atrophy in this population may be associated with advanced physiological aging, but is probably not caused by elevated BP.

White matter lesions (WML) are a frequent finding on brain magnetic resonance imaging scans. Elevated blood pressure (BP) is consistently identified as risk factor for WML. However, it is unknown whether BP still is associated with WML in patients with manifest vascular disease. The aim of this cross-sectional study was to investigate associations between BP and WML in patients with manifest vascular disease. A total of 1030 patients with vascular disease (cerebrovascular disease (23%), coronary heart disease (59%), peripheral arterial disease (23%), abdominal aortic aneurysm (9%)) from the Second Manifestations of Arterial Disease study were included. WML volume was calculated using an automated quantitative volumetric method and subsequently divided into quartiles. We investigated associations between BP and WML and examined whether relations between BP and WML were modified by the localization of the symptomatic site or presence of diabetes. Participants had a mean age of 58.7 years. Median volume of WML was 1.70 ml. Mean BP was 141/82 mmHg and 69% suffered hypertension. No significant associations between systolic BP, diastolic BP, mean arterial pressure (MAP) or hypertension presence and moderate or large WML volumes were present. The relation between BP and WML was not modified by the localization of vascular disease or diabetes presence. Among patients with manifest vascular disease, BP was not associated with the presence of WML, irrespective of the presence of diabetes or the localization of vascular disease.

Objectives: Albuminuria and decreased estimated glomerular filtration rate (eGFR) are associated with increased cardiovascular risk, but do not necessarily coexist and have different pathophysiological mechanisms. This study aims to evaluate separate and combined effects of decreased eGFR and albuminuria on the occurrence of vascular diseases and mortality in patients with vascular disease., Design: Prospective cohort study., Setting: University Medical Center Utrecht, the Netherlands., Subjects and Main Outcome Measures: 2600 patients with vascular disease were followed for vascular events, vascular and all-cause mortality. Cox regression analysis was used to calculate hazard ratios (HRs) according to eGFR (MDRD) and albuminuria (albumin-to-creatinine ratio >3 mg mmol(-1))., Results: In this population, 14.0% had albuminuria, 15.6% had eGFR <60 ml min(-1) 1.73 m(-2) and 5.2% had both. Nonalbuminuric decreased eGFR and albuminuria with normal eGFR generated moderately increased risks on all outcomes. eGFR <60 ml min(-1) 1.73 m(-2) without albuminuria mainly influenced the risk of vascular events (HR 1.50; 1.05-2.15) whilst albuminuria with eGFR >or=60 ml min(-1) 1.73 m(-2) principally affected all-cause mortality (HR 1.53; 1.04-2.26). The combination of eGFR <60 ml min(-1) 1.73 m(-2) and albuminuria was associated with an increased risk for vascular events (HR 2.27; 1.54-3.34), vascular mortality (HR 2.22; 1.40-3.52) and all-cause mortality (HR 1.84; 1.25-2.69). Comparable results were found in additional analyses amongst 759 diabetic patients., Conclusions: The combination of decreased eGFR with albuminuria is associated with the highest risks of vascular events, vascular and all-cause mortality in patients with vascular diseases. To adequately estimate vascular risk associated with impaired renal function, both eGFR and urinary albumin should be considered.

Objective: To evaluate the feasibility of a web-based coaching programme for vascular risk factor treatment, to describe the patterns of use and to measure changes in risk factors., Methods: Patients with a clinical manifestation of arterial disease and Internet access were asked to participate in the nurse-led Internet-based risk factor management programme. At the first clinic visit, a personalized action plan was made for the treatment of risk factors. Patients were instructed on communication with a specialized nurse through Internet and encouraged to enter self-measured risk factor levels at their personalized website. The nurse practitioner replied on working days and gave feedback, support, and recommendations on lifestyle and medical treatment. After 6 months, risk factors were re-measured., Results: Fifty patients participated, 70% were overweight, 64% had hypertension, 42% hyperlipidemia, and 24% smoked at baseline. During 6 months, the log-in average at the individual website was 35 times per patient (1.3 log-ins/week); while the nurse practitioner logged-in at the overall website 23 times/week. The website was hardly used by five patients. Most e-mail messages were sent by patients for hypertension (211 times) and obesity (203 times), whereas the nurse practitioner sent nearly twice as many e-mail messages for hypertension (400 times) and obesity (455 times). The level of most risk factors decreased and the fraction of achieved treatment goals increased (blood pressure from 36 to 58%, LDL-cholesterol from 58 to 64%, glucose from 64 to 82%)., Conclusions: A web-based vascular risk factor intervention programme is feasible; it is frequently used by patients and suitable to decrease the level of several risk factors. It has the promise of being an efficacious intervention for risk factor sanitation in patients with symptomatic vascular disease., Practice Implications: An Internet-based individualised risk management programme could make patients aware of their self-management capability and may contribute to risk factor reduction.

Objective: Abdominal obesity and its associated metabolic consequences are major determinants for the development of vascular disease. Fat tissue close to arteries may also directly affect atherogenesis. The study examined whether intra-abdominal fat accumulation is an independent determinant of infrarenal aortic diameter in patients with clinically evident arterial disease. The relationship between metabolic syndrome and infrarenal aortic diameter was also assessed in this patient group., Methods: Cross-sectional study was done of 2726 patients with clinically evident arterial disease enrolled in the Second Manifestations of ARTerial Disease (SMART) study. Intra-abdominal fat was measured with ultrasonography and by measuring waist circumference. Metabolic syndrome was defined according to the Adult Treatment Panel III. The maximal anteroposterior diameter of the infrarenal aorta was measured using ultrasonography. The relation between intra-abdominal fat, metabolic syndrome, and infrarenal aortic diameter was determined with linear regression analyses and adjusted for age, sex, height, and smoking., Results: Infrarenal aortic diameters (mm) increased across quartiles of intra-abdominal fat derived by ultrasonography (quartile 4, 19 +/- 7 mm vs quartile 1, 17 +/- 5 mm; adjusted beta, 1.34; 95% confidence interval [CI], 0.73-1.94) and across quartiles of waist circumference (quartile 4, 19 +/- 7 mm vs quartile 1, 17 +/- 5 mm; adjusted beta, 1.43; 95% CI, 0.82-2.04). Patients with metabolic syndrome had slightly larger infrarenal aortic diameters (18 +/- 7 mm vs 17 +/- 6 mm; adjusted beta, 0.70; 95% CI, 0.27-1.13) compared with those without metabolic syndrome., Conclusions: Intra-abdominal fat accumulation and metabolic syndrome are associated with larger infrarenal aortic diameters in patients with clinically evident arterial disease. These data may indicate a role for intra-abdominal fat in the development of larger aortic diameters.

Objective: Given the large number of patients at high risk of vascular events, new strategies are needed to reduce vascular risk. We investigated whether self-efficacy promotion could change self-efficacy levels in patients with vascular diseases and whether baseline self-efficacy and changes in self-efficacy were related to changes in vascular risk factors., Methods: One hundred fifty-three recently referred patients with symptomatic vascular diseases (cerebrovascular, abdominal, or peripheral arterial) participated in a randomized trial investigating the effect of nursing care, as compared with usual care, on vascular risk factors. Nursing care consisted of self-efficacy promotion and medical treatment of vascular risk factors. Self-efficacy and vascular risk factors (smoking, BMI, waist, blood pressure, lipid, and glucose levels) were measured at baseline and after 1 year., Results: While total self-efficacy did not change over the 1-year intervention period in either treatment group, self-efficacy in choosing healthy food (mean +0.4+/-1.4, p-value 0.01) and in doing extra exercise (mean +0.3+/-1.3, p-value 0.03) increased in the intervention group. No relation was seen between baseline total self-efficacy or change in composite self-efficacy and change in vascular risk factors., Conclusion: The nursing intervention did not influence total self-efficacy but did improve self-efficacy in choosing healthy food and doing extra exercise. Change in composite self-efficacy was not related to change in vascular risk factors in patients at high risk of developing (new) cardiovascular diseases., Practice Implications: Influencing self-efficacy in choosing healthy food and doing extra exercise could be incorporated in vascular risk reduction programs in addition to medical treatment of vascular risk factors.

Background: Physical activity can influence insulin sensitivity and metabolic syndrome (MetS) independent of weight loss. Therefore, we investigated the independent effect of leisure-time physical activity on the prevalence of MetS and insulin resistance in patients with manifest arterial disease and the role of body fat and fat distribution on this relationship., Methods: Data were collected from the Second Manifestations of ARTerial disease study, an ongoing prospective cohort study of patients with manifest vascular disease or vascular risk factors at the University Medical Center Utrecht. Data of 1097 patients, mean age 58.3 +/- 10.4 years, with clinically manifest arterial disease were used. Information on leisure-time physical activity (sporting or other physical exercise) during the past year was collected using a questionnaire. Patients were classified according to the time spent doing leisure-time physical activities: 0 metabolic equivalent (MET)/h per week (64%), 1.0 to 14.9 MET/h per week (16%), and >15.0 MET/h per week (20%)., Results: The prevalence of MetS was markedly lower (20%) in physically active patients (>15 MET/h per week active) than in physically inactive patients (36%; odds ratio [OR] 0.50, 95% confidence interval [CI] 0.33-0.75) after adjustment for age, sex, body mass index, and smoking. After adjustment for age, sex, waist circumference, and smoking, the OR of having MetS remained essentially the same (OR 0.59, 95% CI 0.38-0.90). Patients who were active (>15 MET/h per week active) had a considerable lower risk of insulin resistance (homeostasis model assessment determined insulin resistance >2.38) than inactive patients (OR 0.40, 95% CI 0.25-0.64) after adjustment for age, sex, body mass index, and smoking., Conclusions: Patients with manifest arterial disease who are physically active are less likely to have MetS and insulin resistance than physically inactive patients, although body weight is comparable between the groups.

Background: Adiponectin is considered to have anti-inflammatory, insulin-sensitizing, and antiatherosclerotic properties. In the present prospective study, the relationship between metabolic syndrome (Adult Treatment Panel III) and adiponectin plasma levels and the relationship between plasma adiponectin levels and future cardiovascular events were investigated., Methods: A case-cohort study of 431 patients with clinical evident vascular disease from the Second Manifestations of ARTerial Disease study. The relationship between adiponectin plasma levels and new vascular events was investigated with Cox regression, adjusted for potential confounders and effect modifiers (age, sex, renal function [modification of diet in renal disease], body mass index, high sensitive C-reactive protein, use of angiotensin converting enzyme-inhibition and/or AII antagonists, and presence of metabolic syndrome or impaired renal function)., Results: Plasma adiponectin levels were lower in patients with metabolic syndrome as compared with patients without (7.9 +/- 0.3 vs 5.2 +/- 0.3 microg/mL) and decreased with the number of components. During a mean follow-up of 2.3 years, 216 patients had a new cardiovascular event. Lower adiponectin plasma levels were associated with a lower risk for future cardiovascular events (hazard ratio 0.50, 95% confidence interval 0.25-0.99). This relationship was not influenced by renal function, body mass index, and renin-angiotensin system-blocking agents or modified by metabolic syndrome and impaired renal function., Conclusion: In patients with clinical evident vascular disease, lower adiponectin levels were associated with a lower cardiovascular risk. Therefore, it may be hypothesized that the potential antiatherosclerotic properties of adiponectin do not apply for patients with already established vascular disease.

Objectives: Vitamin K is an important co-factor in the production of proteins that inhibit vascular calcification. A low dietary Vitamin K intake has been associated with aortic and coronary calcifications and an elevated cardiovascular risk. Calcifications in the arteries of the breasts have also been associated with cardiovascular risk, but whether there is a relation with a low Vitamin K intake has not yet been studied., Methods: We conducted a cross-sectional study among 1689 women, aged 49-70 years. Dietary Vitamins K1 and K2 intake was calculated from a validated food frequency questionnaire. Breast arterial calcifications (BAC) were assessed on standard screening mammograms by two independent radiologists. With a general linear model mean Vitamins K1, K2 and Vitamin K2 subtypes were calculated for women with BAC and without, adjusted for age, smoking, diabetes, intake of saturated fat, mono-unsaturated fat, poly-unsaturated fat and protein- and calcium-intake., Results: BAC was less common in the highest (9%) quartile of Vitamin K2 intake, compared to the lowest (13%) (OR 0.7, 95% CI 0.5-1.1) and not different across quartiles of Vitamin K1 intake. Mean Vitamin K2 levels and mean levels of Vitamin K2 subtypes MK-5 through MK-10 were lower in the participants with BAC (p=0.01) compared to participants without BAC. However, after adjustment for aging, smoking, diabetes and dietary factors the association of mean Vitamin K2 intake with BAC was no longer significant., Conclusion: Calcifications in breast arteries are not associated with a lower dietary intake of Vitamin K.

Background: Patients with manifest vascular disease are at high risk of a new vascular event or death. Modification of classical risk factors is often not successful. We determined whether the extra care of a nurse practitioner could be beneficial to the cardiovascular risk profile of high-risk patients., Design: We conducted a randomized, controlled trial based on the Zelen design., Methods: Two hundred and thirty-six patients with manifestations of a vascular disease and who had two or more modifiable vascular risk factors were pre-randomized to receive treatment by a nurse practitioner plus usual care or usual care alone. After 1 year, risk factors were remeasured. The primary endpoint was achievement of treatment goals for blood pressure, lipid, glucose and homocysteine levels, body mass index, and smoking., Results: Of the pre-randomized patients, 95 of 119 (80%) in the intervention group and 80 of 117 (68%) in the control group participated in the study. After a mean follow-up of 14 months, the patients in the intervention group achieved significantly more treatment goals than did the patients in the control group (systolic blood pressure 63 versus 37%, total cholesterol 79 versus 61%, low density lipoprotein-cholesterol 88 versus 67%, and body mass index 38 versus 24%). Medication use was increased in both groups and no differences were found in patients' quality of life (SF-36) at follow-up., Conclusion: Treatment delivered by nurse practitioners, in addition to a vascular risk factor screening and prevention program, resulted in a better management of vascular risk factors than usual care alone in vascular patients after 1-year follow-up.

Purpose: To retrospectively investigate which characteristics are related to total arterial blood flow to the brain in patients with symptomatic vascular disease., Materials and Methods: The study was approved by the ethics committee of the authors' institution, and written informed consent was obtained. The total volume flow rate (tVFR) values in the internal carotid arteries and the basilar artery in 636 patients (536 men, 100 women; mean age, 58 years) with symptomatic vascular disease were measured with two-dimensional phase-contrast magnetic resonance (MR) angiography. Reference tVFR values in the general population were obtained from previous research involving 158 subjects (73 men, 85 women; mean age, 60 years)., Results: A higher tVFR was found in patients with symptomatic vascular disease, but this association was statistically significant in only those patients in the 7th decade of life. The mean tVFR decreased with increasing age (-3.4 mL/min per year; 95% confidence interval [CI]: -4.3, -2.5). Diabetes (-27.6 mL/min; 95% CI: -52.6, -2.6) and increasing body mass index (BMI) (-2.8 mL/min per BMI unit; 95% CI: -5.3, -0.2) were associated with lower tVFR. Patients with vascular disease in a cerebral location had lower tVFR values (-39.7 mL/min; 95% CI: -65.1, -14.3) than did patients with symptomatic vascular disease elsewhere in the vascular tree., Conclusion: Patients with symptomatic vascular disease had slightly higher arterial blood flow to the brain compared with the general population. The tVFR decreased with increasing age and increasing BMI, and patients with diabetes had lower tVFR values than did those without diabetes. Patients with vascular disease in a cerebral location had lower tVFR values than did those with symptomatic vascular disease at other arterial sites., (RSNA, 2006)

Objective: Patients with established cardiovascular disease are at high risk of developing new vascular events or death. This risk can be reduced by lifelong treatment of risk factors and by permanent changes in lifestyle. Self-efficacy is important for achieving behavior change by self-management. The self-efficacy of different vascular risk factors subgroups in patients with clinical manifestations of atherosclerotic vascular diseases was investigated., Methods: From January 2001 to September 2003, 192 patients with recently established clinically manifest atherosclerotic disease with > or = 2 modifiable vascular risk factors were selected for the study. The mean self-efficacy scores were calculated for vascular risk factors (age, sex, vascular disease, weight, diabetes mellitus, smoking behavior, hypercholesterolemia, hypertension, and hyperhomocysteinemia)., Results: Diabetes, overweight, and smoking, but none of the other risk factors, were significantly associated with the level of self-efficacy in these patients., Conclusions: Patients with vascular diseases appear to have high levels of self-efficacy regarding medication use, exercise, and controlling weight. In patients with diabetes, overweight, and in smokers, self-efficacy levels were lower., Practice Implications: In nursing care and research on developing self-efficacy based interventions, lower self-efficacy levels can be taken into account for specific vascular patient groups.

Objectives: To assess the relationship between total plasma homocysteine (tHcy) level and cognitive function in patients with manifest arterial disease., Design: Cross-sectional., Setting: Patients with symptomatic cerebrovascular disease, cardiovascular disease, peripheral arterial disease, or abdominal aortic aneurysm included in the Second Manifestations of ARTerial disease study, a single-center, longitudinal study with an extensive screening program at baseline., Participants: Three hundred forty-five consecutively included patients, mean age 59., Measurements: The patients underwent an extensive neuropsychological test. The cognitive domains assessed were memory, executive function, attention, and visuoperception and construction. Each raw score was transformed into standardized z-scores, and a sum score for global cognitive function was determined. Risk factors and vascular damage were measured in detail., Results: Linear regression showed that elevated levels of tHcy were related to lower global cognitive function (beta=-0.065, 95% confidence interval (CI)=-0.116 to -0.013) and, more specifically, lower performance on memory (beta=-0.078, 95% CI=-0.155 to -0.002), attention (beta=-0.079, 95% CI=-0.163 to -0.005), and visuoperception and construction (beta=-0.125, 95% CI=-0.236 to -0.014) per standard deviation increase in tHcy (SD=6.4 mol/L), after adjustment for age, sex, educational level, extent of atherosclerosis, and location of vascular disease. Silent cerebral infarcts did not influence this relationship., Conclusion: A relationship was found between tHcy levels and cognitive function that was independent of extent and location of arterial disease. The results suggest that vascular mechanisms are not responsible for the relationship between tHcy and cognitive function.

Background and Purpose: Silent infarcts are frequently found on MRIs of brains of healthy elderly persons (aged >60 years). The purpose of this study was to investigate the prevalence and determinants of silent infarcts in a population of patients with clinically manifest vascular disease., Methods: To detect silent infarcts, MR images were made in 308 participants of the Second Manifestations of ARTerial disease (SMART) study (mean age, 58 years) without prior stroke or transient ischemic attack. These are patients referred to the University Medical Center Utrecht because of atherosclerotic vascular disease. Risk factors were assessed by questionnaire and by physical, ultrasonographic, and laboratory examinations., Results: Silent infarcts were found in 51 patients (17%). Most infarcts (62%) were located in white matter, 20% in basal ganglia, 14% in brain stem and cerebellum, and 4% in cortical area. Categorical determinants for presence of silent infarct(s) that remained (borderline) significant after adjustment for age were hypertension (odds ratio [OR]=2.2; 95% CI, 1.2 to 4.2), abdominal aortic aneurysm (OR=2.4; 95% CI, 0.9 to 6.4), severe renal failure (OR=7.3; 95% CI, 2.1 to 25.2), and hyperhomocysteinemia (OR=2.6; 95% CI, 1.1 to 5.9)., Conclusions: Patients with manifest vascular disease are at risk for silent infarcts at a younger age. In particular, patients with the aforementioned risk factors should be considered for treatment or (secondary) prevention.

In a cohort of 12,239 women aged 50-69, who participated in a population-based breast cancer screening project (DOM-project) in Utrecht, The Netherlands, as well as being coded for micro-calcifications indicative of breast cancer, the mammograms were also coded for arterial calcifications. This allowed for a secondary analysis of associations between breast arterial calcification (BAC) and the occurrence of arteriosclerosis-associated morbidity (ie diabetes, hypertension, albuminuria, stroke, thrombosis and myocardial infarction). Arterial calcifications were seen on screening mammograms in 9.1% of the women. Significant relations were found between BAC and albuminuria [Relative risk (RR) 2.7; 95% CI 1.0-7.0], BAC and hypertension (RR 1.1; 95% CI 1.0-1.3), transient ischaemic attack (TIA)/stroke (RR 1.4; 95% CI 1.1-1.8), thrombosis (RR 1.5; 95% CI 1.0-2.2) and myocardial infarction (RR 1.8; 95% CI 1.1-2.9). In addition BAC were associated with diabetes in the oldest age-group (RR 1.7; 95% CI 1.2-2.4). All relations were adjusted for age, smoking, parity and Quetelet index. The results of the present study show that BAC as detected on breast cancer screening mammograms are associated with disorders related to increased or accelerated arterio-sclerosis. Where increased parity is associated with a decrease in breast cancer risk, parity increases the occurrence of BAC. The present study suggests that breast-cancer screening mammograms may allow for the early detection of enhanced cardiovascular disease risk among otherwise healthy women.

Objectives A remarkable variation exists in the cardiometabolic consequences of obesity. We evaluated the separate and combined effects of adiposity and cardiometabolic dysfunction on the occurrence of cardiovascular events and mortality in patients with vascular disease. Methods We prospectively followed 5231 patients with a history of clinical cardiovascular disease without diabetes from the Second Manifestations of ARTerial disease (SMART) study. Patients were classified according to body mass index and cardiometabolic function. The presence of cardiometabolic dysfunction was defined as ≥ 3 of the modified National Cholesterol Education Program (NCEP) metabolic syndrome criteria (waist circumference replaced by elevated C-reactive protein). Cox proportional-hazards analysis was used to estimate HRs for cardiovascular events and mortality. Results The prevalence of cardiometabolic dysfunction was 40% in normal weight, 58% in overweight and 75% in obese patients. During a median follow-up of 6.1 years, 769 patients died and 705 patients experienced a major cardiovascular event. In the absence of cardiometabolic dysfunction, overweight (HR 1.18, 95% CI 0.90 to 1.55) and obese patients (HR 0.93, 95% CI 0.53 to 1.64) were not at increased risk of recurrent major cardiovascular events compared with normal weight patients without cardiometabolic dysfunction. An increased cardiovascular risk was observed in patients with cardiometabolic dysfunction and normal weight (HR 1.58, 95% CI 1.23 to 2.04), overweight (HR 1.35, 95% CI 1.07 to 1.70) and obesity (HR 1.50, 95% CI 1.12 to 2.00) compared with normal weight patients without cardiometabolic dysfunction. A similar pattern was observed for vascular and all-cause mortality. Conclusions In patients with vascular disease, the cardiometabolic consequences of adiposity rather than adiposity per se increase the risk of recurrent cardiovascular events and mortality. [ABSTRACT FROM AUTHOR]

Aims:Adiposity is associated with an increased but also with a decreased risk for successive vascular events or mortality in patients with different manifestations of vascular disease. In this study we directly compare the risk of general adiposity or abdominal obesity on the occurrence of new vascular events or mortality in these patients.Methods:Patients with cerebrovascular disease (CVD; n=973), coronary artery disease (CAD; n=2339) or peripheral arterial disease (PAD; n=894) were prospectively followed for the occurrence of a vascular event or death. The median follow-up was 4.5 years. Adiposity was assessed with body mass index (BMI), waist circumference (WC) and determination of intra-abdominal fat through ultrasound. Cox proportional hazards models were used to evaluate the risk for new vascular events, vascular mortality and all-cause mortality.Results:CAD patients had a 12% increased risk for vascular mortality with 1 BMI unit increase (hazard ratio (HR) 1.12; 95% confidence interval (CI) 1.05-1.20) and a 25% increased risk with 1cm increase in intra-abdominal adipose tissue (HR 1.25; 95% CI 1.12-1.39). The risk for all-cause mortality was increased by 3% (HR 1.03; 95% CI 1.01-1.05) with 1 cm increase in WC and was increased by 15% (HR 1.15; 95% CI 1.06-1.25) with 1 cm increase in intra-abdominal adipose tissue. In PAD patients there was an inverse relationship between BMI and vascular mortality (HR 0.93; 95% CI 0.87-0.98) and all-cause mortality (HR 0.90; 95% CI 0.86-0.94). In CVD patients there was no relation between obesity and vascular events or mortality.Conclusion:General adiposity is associated with an increased risk for vascular mortality in CAD patients and a decreased risk for (vascular) mortality in PAD patients. [ABSTRACT FROM AUTHOR]