Manifestations Of ARTerial Disease Study Research Articles

Association of body mass index and waist circumference with long-term mortality risk in 10,370 coronary patients and potential modification by lifestyle and health determinants.

Body adiposity is known to affect mortality risk in patients with coronary artery disease (CAD). We examined associations of body mass index (BMI) and waist circumference (WC) with long term mortality in Dutch CAD patients, and potential and effect modification of these associations by lifestyle and health determinants. 10,370 CAD patients (mean age ∼65 y; 20% female; >80% on cardiovascular drugs) from the prospective Alpha Omega Cohort and Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study were included. Cox models were used to estimate categorical and continuous associations (using restricted cubic splines) of measured BMI and WC with all-cause and cardiovascular mortality risk, adjusting for age, sex, smoking, alcohol, physical activity and educational level. Analyses were repeated in subgroups of lifestyle factors (smoking, physical activity, diet quality), education and health determinants (diabetes, self-rated health). During ∼10 years of follow-up (91,947 person-years), 3,553 deaths occurred, including 1,620 from cardiovascular disease. U-shaped relationships were found for BMI and mortality risk, with the lowest risk for overweight patients (BMI ∼27 kg/m2). For obesity (BMI ≥30), the HR for all-cause mortality was 1.31 (95% CI: 1.11, 1.41) in male patients and 1.10 (95% CI: 0.92, 1.30) in female patients, compared to BMI 25-30 kg/m2. WC was also non-linearly associated with mortality, and HRs were 1.18 (95%CI:1.06, 1.30) in males and 1.31 (95%CI:1.05, 1.64) in females for the highest vs. middle category of WC. Results for cardiovascular mortality were mostly in line with the results for all-cause mortality. U-shaped associations were found in most subgroups, associations were moderately modified by physical activity, smoking and educational level. CAD patients with obesity and a large WC were at increased risk of long-term CVD and all-cause mortality, while mildly overweight patients had the lowest risk. These associations were consistent across subgroups of patients with different lifestyles and health status.

C-Reactive Protein and Risk of Cardiovascular Events and Mortality in Patients with Various Cardiovascular Disease Locations

Anti-inflammatory drugs reduce the risk of cardiovascular events in patients with coronary artery disease (CAD), but less is known about the relation between inflammation and outcomes in patients with cerebrovascular disease (CeVD), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA). This study assessed the association between C-reactive protein (CRP) and clinical outcomes in patients with CAD (n=4,517), CeVD (n=2,154), PAD (n=1,154), and AAA (n=424) from the prospective Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease study. The primary outcome was recurrent cardiovascular disease (CVD), defined as myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes were major adverse limb events and all-cause mortality. Associations between baseline CRP and outcomes were assessed using Cox proportional hazards models adjusted for age, sex, smoking, diabetes mellitus, body mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, and glomerular filtration rate. Results were stratified by CVD location. During a median follow-up of 9.5years, 1,877 recurrent CVD events, 887 major adverse limb events, and 2,341 deaths were observed. CRP was independently associated with recurrent CVD (hazard ratio [HR] per 1mg/L 1.08, 95% confidence interval [CI] 1.05 to 1.10), and all secondary outcomes. Compared with the first quintile of CRP, HRs for recurrent CVD were 1.60 (95% CI 1.35 to 1.89) for the last quintile ≤10mg/L and 1.90 (95% CI 1.58 to 2.29) for the subgroup with CRP >10mg/L. CRP was associated with recurrent CVD in patients with CAD (HR per 1mg/L 1.08, 95% CI 1.04 to 1.11), CeVD (HR 1.05, 95% CI 1.01 to 1.10), PAD (HR 1.08, 95% CI 1.03 to 1.13), and AAA (HR 1.08, 95% CI 1.01 to 1.15). The association between CRP and all-cause mortality was stronger for patients with CAD (HR 1.13, 95% CI 1.09 to 1.16) than for patients with other CVD locations (HRs 1.06 to 1.08; p=0.002). Associations remained consistent beyond 15years after the CRP measurement. In conclusion, greater CRP is independently associated with an increased risk of recurrent CVD and mortality, irrespective of previous CVD location.

External validation of bleeding risk models for the prediction of long-term bleeding risk in patients with established cardiovascular disease

ObjectiveThe long-term predictive performance of existing bleeding risk models in patients with various manifestations of cardiovascular disease (CVD) is not well known. This study aims to assess and compare the performance of relevant existing bleeding risk models in estimating the long-term risk of major bleeding in a cohort of patients with established CVD. MethodsSeven existing bleeding risk models (PRECISE-DAPT, DAPT, Ducrocq et al, de Vries et al, S2TOP-BLEED, Intracranial B2LEED3S and HAS-BLED) were identified and externally validated in 7,249 patients with established CVD included in the Utrecht Cardiovascular Cohort–second manifestations of arterial disease study. Predictive performance was assessed in terms of discrimination and calibration, both at 10 years and the original prediction horizon of the models. Major bleeding was defined as Bleeding Academic Research Consortium type 3 or 5. ResultsAfter a median follow-up of 8.4 years (interquartile range 4.5-12.5), a total of 233 (3.2%) major bleeding events occurred. C-statistics for discrimination at 10 years ranged from 0.53 (95%CI 0.49-0.57) to 0.64 (95%CI 0.60-0.68). Calibration plots after recalibration to 10 years showed best agreement between predicted and observed bleeding risk for De Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. ConclusionsThe performance of existing bleeding risk models to predict long-term bleeding in patients with CVD varied. Discrimination and calibration were best for the models of de Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. Of these, recalibrated models requiring the least predictors may be preferred for use to personalize prevention with antithrombotic therapy.

The association between a genetic variant in the SULF2 gene, metabolic parameters and vascular disease in patients at high cardiovascular risk.

To determine the relationship between rs2281279, metabolic parameters and vascular events, and type 2 diabetes mellitus (T2DM) in patients at high cardiovascular risk and whether APOE genotype modifies this relationship. Patients (n = 4386) at high cardiovascular risk from the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease study were stratified according to their imputed rs2281279 genotype: AA (n = 2438), AG (n = 1642) and GG (n = 306). Effects of rs2281279 on metabolic parameters, vascular events and T2DM were analyzed with linear regression and Cox models. There was no relationship between imputed rs2281279 genotype and triglycerides, non-high-density lipoprotein (HDL)-cholesterol, insulin and quantitative insulin sensitivity check index. During a median follow-up of 11.8 (IQR, 9.3-15.5) years, 1026 cardiovascular events and 320 limb events occurred. The presence of the G allele in rs2281279 did not affect the risk of vascular events [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.94-1.14] or limb events (HR, 0.92; 95% CI, 0.77-1.10). The presence of the G allele in rs2281279 did not affect the risk of T2DM (HR, 1.09; 95% CI, 0.94-1.27). The presence of the minor G allele of rs2281279 was associated with a beneficial risk profile in ε2ε2 patients, but not in ε3ε3 patients. Imputed rs2281279 genotype is not associated with metabolic parameters and does not increase the risk of vascular events or T2DM in patients at high risk for cardiovascular disease.

Visceral adipose tissue quantity and dysfunction and the occurrence of major bleeding in patients with established cardiovascular disease

ObjectivesTo determine the association between both visceral fat quantity and adipose tissue dysfunction, and major bleeding in patients with established cardiovascular disease. MethodsPatients from the Second Manifestations of ARTerial disease study with established cardiovascular disease were included. Visceral fat was measured using ultrasound and adipose tissue dysfunction was depicted using metabolic syndrome criteria (revised National Cholesterol Education Program). Cox regression models were fitted to study the relation with major bleeding defined as Bleeding Academic Research Consortium (BARC) type 3 or 5, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding. Sensitivity analyses were performed using C-reactive protein levels to reflect adipose tissue dysfunction. ResultsIn 6927 patients during a median follow up of 9.2 years, a total of 237 BARC type 3 or 5 bleedings and 224 ISTH major bleedings were observed. Visceral fat quantity was not related to major bleeding (HR 1.01, 95%CI 0.88–1.16 for BARC type 3 or 5 bleeding and HR 1.00, 95%CI 0.87–1.15 for ISTH major bleeding), nor was metabolic syndrome (HR 0.97, 95%CI 0.75–1.26 for BARC type 3 or 5 bleeding and HR 0.98, 95%CI 0.75–1.28 for ISTH major bleeding). Sensitivity analyses using C-reactive protein levels showed similar results. No effect modification was observed by sex, antithrombotic therapy, presence of metabolic syndrome or diabetes. ConclusionIn patients with cardiovascular disease, no association was found between visceral fat quantity measured with ultrasound or measures of adipose tissue dysfunction and the risk of major bleeding, irrespective of antithrombotic agent use.

Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus

AimTo evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies.MethodsWe included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model.ResultsIn patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95–1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99–1.14)].ConclusionThere is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.

Risk Factors for Recurrent Cardiovascular Events Before Age 65 Years or Within 2.5 Years of a Recent First Cardiovascular Event

The aim of this study was to quantify the relation between classical risk factors (smoking, diabetes, BMI, waist circumference, blood pressure, and lipids), risk factor targets, and risk of recurrent major atherosclerotic cardiovascular events (MACE). This was first done for recurrent MACE ≤65years in patients aged <60years and second for recurrent MACE ≤2.5years after a first cardiovascular event. Data were used from the Second Manifestations of Arterial Disease study (n= 5,115), a prospective cohort of patients with a recent (≤1year) first cardiovascular event. During follow-up, 746 recurrent MACE occurred. Smoking (hazard ratio [HR] 1.43, 95% CI 1.11 to 1.84), diabetes (HR 1.83, 95% CI 1.11 to 1.84), diastolic blood pressure (>90 vs 70 to 90mm Hg, HR 1.54, 95% CI 1.15 to 2.07), and high-density lipoprotein cholesterol (≤1.0 vs >1.0mmol/L, HR 1.34, 95% CI 1.03 to 1.76) were related to increased risk of recurrent MACE ≤65years in patients aged <60years. Smoking (HR 1.65, 95% CI 1.23 to 2.22), physical inactivity (highest vs lowest tertile, HR 1.48, 95% CI 1.05 to 2.09), body mass index (per kg/m2, HR 1.04, 95% CI 1.00 to 1.08), diastolic blood pressure (>90 vs 70 to 90mm Hg, HR 1.61, 95% CI 1.17 to 2.21), low-density lipoprotein cholesterol (per mmol/L, HR 1.18, 95% CI 1.02 to 1.37), and non-high-density lipoprotein cholesterol (per mmol/L, HR 1.15, 95% CI 1.03 to 1.28) were related to recurrentMACE ≤2.5years of follow-up. In conclusion, in patients with a recent cardiovascular event, smoking, blood pressure, and lipids are related to increased risk of recurrent cardiovascular events at young age or within a short time span, and intensive treatment of modifiable risk factors may contribute to prevent recurrent MACE in these patients.

Low-Density Lipoprotein Cholesterol, Non–High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease

Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5years (interquartile range 3.4 to 9.9years). Adjusted hazard ratios (HRs) of MACEper 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude.

Physical Activity and Vascular Events and Mortality in Patients with Vascular Disease.

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. 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. 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. 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.

The combined use of aspirin, a statin, and blood pressure–lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease

Patients with established coronary artery disease (CAD) are likely to receive a combination of aspirin, a statin, and blood pressure (BP)-lowering agents. Combining these pharmacologic agents into a cardiovascular combination pill, such as a polypill, could be considered to reduce prescription gaps and nonadherence in high-risk patients. We aimed to evaluate the effect of the concomitant use of aspirin, a statin, and BP-lowering agent(s) in patients with CAD on vascular morbidity and mortality in current clinical practice in an observational study to provide insights in the combination pill concept related to feasibility and applicability. In total, 2,706 patients with CAD enrolled in the Second Manifestations of ARTerial disease study were followed for the occurrence of a subsequent vascular event (ie, myocardial infarction, ischemic cerebrovascular accident, vascular death) and all-cause mortality. The relationship between combination therapy and cardiovascular events and all-cause mortality was assessed using Cox proportional hazards regression models to calculate hazards ratios (HRs) with a 95% CI. Both covariate and propensity score adjusting methods were used to reduce confounding by indication. A combination of aspirin, a statin, and ≥1 BP-lowering agent(s) was used by 67% of the patients. During a median of 5.0 years (interquartile range 2.4-10.2 years), 347 vascular events occurred and 162 patients died. Combination therapy with aspirin, statin, and ≥1 BP-lowering agent was associated with a lower risk of myocardial infarction (HR 0.68, 95% CI 0.49-0.96), ischemic cerebrovascular accident (HR 0.37, 95% CI 0.16-0.84), composite vascular end point (HR 0.66, 95% CI 0.49-0.88), vascular mortality (HR 0.53, 95% CI 0.33-0.85), and all-cause mortality (HR 0.69, 95% CI 0.49-0.96) compared with the absence of combination therapy, after adjusting for confounding covariates in a propensity score. The use of 1 or only 2 components of combination therapy was associated with a higher risk for cardiovascular events compared with the combined use of aspirin, a statin, and ≥1 BP-lowering agent(s). Two-thirds of the patients with CAD use a combination of aspirin, a statin, and ≥1 BP-lowering agent(s), components of a cardiovascular fixed-dose combination pill. Combination therapy with these agents is associated with a lower risk of vascular events and total mortality. Although treatment effect in observational studies should be interpreted with caution, the results of this study support supposed benefits from combination therapy. However, the effect of fixed-dose combination pill on clinical outcome needs to be demonstrated in randomized clinical trials.

Asymptomatic Carotid Artery Stenosis and the Risk of Ischemic Stroke According to Subtype in Patients With Clinical Manifest Arterial Disease

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. 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. 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). 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.

Relation between adiposity and hypertension persists after onset of clinically manifest arterial disease

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. 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. 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. 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.

Is the J-Shaped Curve Related to Vascular Mortality?

To the Editor: We have read recently with interest the article by Dorresteijn et al1 concerning the relationship between blood pressure values and vascular events. The data for this article originate from Second Manifestations of Arterial Disease Study, which was designed to focus on the prevalence and incidence of additional cardiovascular disease in patients who had a previous manifestation of arterial disease or who were at high risk to develop symptomatic arterial disease.2 The authors showed that blood pressure levels below and above 143/82 mm Hg are independent risk factors for recurrent events in patients with symptomatic vascular disease and the relationship between systolic blood pressure (SBP) or diastolic …

Abstract P329: The Use of Polypill Components is Related to Lower Vascular Morbidity Aand Mortality in Patients With Vascular Diseases or Type 2 Diabetes Mellitus

Background and aims Patients with established cardiovascular disease or diabetes mellitus type 2 (DM2) are likely to receive separate treatment of an 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 increase adherence. We evaluated the effect of the concomitant use of aspirin, a statin and BP-lowering agent(s) in patients with vascular diseases or DM2 on vascular morbidity and mortality in current clinical practice. Methods In total 5783 patients with coronary artery disease, cerebrovascular disease, abdominal aortic aneurysm, peripheral arterial occlusive disease or DM2 enrolled in the Second Manifestations of ARTerial disease study were followed/up for the occurerence of a subsequent vascular event (i.e. myocardial infarction (MI), ischaemic cerebrovascular accident (iCVA), vascular death), composite vascular endpoint (combination of previous mentioned) and all-cause mortality. Results In total 2456 (42%) used aspirin, a statin and 1 BP lowering agent. During a median of 5.3 years (interquartile range 2.7-9.3 years), 758 patients experienced a new vascular event and 737 died. Combination therapy with aspirin, statin and ≥1 BP lowering agent was associated with a lower risk of MI (HR 0.77; 95%CI 0.62-0.97), iCVA (HR 0.75; 95%CI 0.52-1.08), vascular mortality (HR 0.56; 95%CI 0.44-0.72), composite vascular endpoint (HR 0.52; 95%CI 0.43-0.63) and all-cause mortality (HR 0.52; 95%CI 0.43-0.63) after adjusting for confounding covariates ( Table 1 ). Table Aspirin, statin and ≥1 BP lowering agents Study endpoint No. of events HR (95%-CI) Coronary Artery Disease I 418 0,79 (0,63-0,97) II 0,77 (0,62-0,95) III 0,77 (0,62-0,95) IV 0,79 (0,63-0,99) PS 0,77 (0,62-0,97) Cerebrovascular accident I 181 0,65 (0,46-0,91) II 0,64 (0,46-0,90) III 0,65 (0,46-0,91) IV 0,78 (0,54-1,13) PS 0,75 (0,52-1,08) Composite Vascular Endpoint I 720 0,73 (0,62-0,86) II 0,72 (0,61-0,85) III 0,73 (0,61-0,86) IV 0,78 (0,65-0,94) PS 0,75 (0,62-0,89) Vascular Mortality I 428 0,59 (0,47-0,75) II 0,62 (0,49-0,78) III 0,60 (0,48-0,76) IV 0,63 (0,49-0,80) PS 0,56 (0,44-0,72) All-cause Mortality I 737 0,54 (0,45-0,65) II 0,56 (0,47-0,67) III 0,56 (0,47-0,68) IV 0,57 (0,47-0,69) PS 0,52 (0,43-0,63) Model I: Crude II: Adjusted for gender, age III: II + additional adjustment for BMI, current smoking, packyears, concommitent cardiovascular disease IV: III + additional adjustment for LDL, systolic BP Propensity Score: composed of gender, age, BMI, current smoking, packyears, concomitant cardiovascular disease, LDL cholesterol and systolic BP Conclusion The combined use of aspirin, statin and at least 1 BP lowering agent was associated with a lower risk of vascular morbidity and mortality in patients with established cardiovascular disease or DM2. Introduction of a polypill in these high risk patients may promote the use of preventive pharmacologic treatment and contribute to better adherence thereby decreasing the risk for vascular morbidity and mortality.

Relation Between Blood Pressure and Vascular Events and Mortality in Patients With Manifest Vascular Disease

Recent studies have challenged the notion that "lower is better" for blood pressure in relation to vascular events and mortality in patients with vascular disease, whereas practice guidelines currently recommend to lower blood pressure to <130/80 mm Hg. We reassessed this J-curved relationship between blood pressure and cardiovascular events and all-cause mortality in patients with various manifestations of vascular disease. For this purpose, 5788 patients with symptomatic vascular disease enrolled in the Secondary Manifestations of Arterial Disease Study were followed-up for the occurrence of new vascular events (ie, myocardial infarction, stroke, or vascular death) and all-cause mortality. During a median of 5.0 years (interquartile range: 2.6-8.1 years), 788 patients experienced a new vascular event, and 779 died. Overall, the covariate-adjusted relationship between mean baseline systolic, diastolic, or pulse pressure and the occurrence of vascular events followed a J-curve with increased event rates above and below the nadir blood pressure of 143/82 mm Hg. A similar nonlinear relationship was found for diastolic pressure and all-cause mortality. Elevated blood pressure was not associated with increased morbidity and mortality in patients with recently diagnosed coronary artery disease, ≥65 years, and having >60 mm Hg pulse pressure. Importantly, especially in these subgroups, low blood pressure could also be a symptom rather than a cause of disease. Blood pressure level below and above 143/82 mm Hg is, thus, an independent risk factor for recurrent events in patients with manifest vascular disease. Uncertainty of whether this association is causal provides a strong rationale for trials evaluating blood pressure treatment targets.

Cerebral Microbleeds on MR Imaging: Comparison between 1.5 and 7T

The detection of microbleeds differs strongly between studies, due to differences in scan protocol. This study aims to compare the visualization of microbleeds with 3D T2*-weighted imaging at 1.5T with 3D dual-echo T2*-weighted imaging at 7T. Thirty-four patients (29 male; mean age, 58 ± 12 years) with atherosclerotic disease from the Second Manifestations of ARTerial Disease study were included. 3D T2*-weighted imaging at 1.5T and dual-echo T2*-weighted imaging at 7T were done in all patients. The presence and number of definite microbleeds were recorded on minimal intensity projections. Inter- and intraobserver reliability was assessed with Cohen κ test and the ICC. The difference in presence and number of microbleeds was tested with the McNemar test and Wilcoxon signed rank test. The interobserver ICC at 7T was 0.61 and the intraobserver ICC was 0.94, whereas at 1.5T the interobserver ICC was 0.50 and the intraobserver ICC was 0.59. Microbleeds were detected in significantly more patients on 7T (50%) than on 1.5T scans (21%) (P = .001). The number of microbleeds was also higher at 7T (median, 0.5; range, 0-5) than on 1.5T (median, 0.0; range, 0-6) (P = .002). 3D dual-echo T2*-weighted imaging at 7T results in better and more reliable detection of microbleeds compared with 3D T2*-weighted imaging at 1.5T.

Trends in vascular risk factors and medication use in patients with various manifestations of vascular diseases or type 2 diabetes mellitus from 1996 to 2007: the Second Manifestations of ARTerial disease study

To investigate time trends in vascular risk factors and medication use for patients referred to a vascular specialist with manifest vascular disease or type 2 diabetes mellitus (DM2). Change in risk factor profile and medication use at referral over a 12-year period was evaluated and compared between patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, and DM2, who participated in the Second Manifestations of ARTerial disease study in the period of 1996-2007. A total of 4731 patients were included (mean age 59±11 years, 75% male) in the period 1996-2007. Obesity (body mass index ≥30 kg/m²) prevalence increased from 14 to 24%, and no change in smoking behavior was observed. The prevalence of hyperlipidemia (total cholesterol ≥4.5 mmol/l or low-density lipoprotein cholesterol ≥2.5 mmol/l) at referral declined from 92% in 1996-1997 to 45% in 2006-2007. The proportion of patients with blood pressure above 140/90 mmHg decreased from 66 to 51%. The use of lipid-lowering, blood pressure-lowering, and antithrombotic medication at referral increased over the observation period. An improvement in risk factor profile was seen in patients referred with manifest vascular disease or DM2 over a 12-year period. Nevertheless, the prevalence of modifiable risk factors is still high leaving patients at elevated vascular risk.

Surgical or Medical Management for Asymptomatic Carotid Stenosis

To the Editor: We read with interest the article by Woo et al published in the May issue of Stroke .1 The authors have studied the contemporary results of carotid endarterectomy (CEA) for 5009 asymptomatic carotid stenosis (ACS) identified in the National Surgical Quality Improvement Program database. They have found that the perioperative stroke, death, and myocardial infarction outcome rates are 0.96%, 0.56%, and 0.22%, respectively. The authors have combined the 0.96% perioperative stroke rates with the 5-year stroke risk after …

Blood Pressure and White Matter Lesions in Patients with Vascular Disease: The SMART-MR Study

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.

Metabolic syndrome and vascular risk in patients with peripheral arterial occlusive disease

Peripheral arterial occlusive disease (PAOD) is associated with a high risk of cardiovascular events. The metabolic syndrome is a frequent condition among patients with manifest vascular disease, but the influence of the metabolic syndrome on cardiovascular events in patients with PAOD is unknown. Also, progression and regression of the metabolic syndrome after follow-up are not extensively studied. The study population consisted of 461 patients with symptomatic PAOD from the Second Manifestations of Arterial Disease study (SMART). Patients underwent vascular screening at baseline and after a mean follow-up of 5.5 +/- 1.3 years. Hazard ratios (HRs) for vascular events according to metabolic syndrome status (updated National Cholesterol Education Program [NCEP] criteria) were calculated using Cox regression analysis. The course of the metabolic syndrome during follow-up and the influence of body mass index (BMI) on development or disappearance of the syndrome were assessed. During follow-up, 91 first vascular events were recorded. Cumulative 3-year survival free from vascular events was 84.7% in metabolic syndrome patients compared to 92.1% in participants without the syndrome. The metabolic syndrome was associated with an increased risk of vascular events (HR 1.51; 1.01-2.30, age- and gender-adjusted). During follow-up, 128 patients died or were lost to follow-up, and of 333 remaining patients, 221 participated in follow-up measurements. The metabolic syndrome disappeared in 16% of patients and was incident in 14% of patients during follow-up. Waist circumference increased with 10 +/- 8 cm in those developing the syndrome. A BMI decrease of 1 kg/m(2) significantly decreased the risk of metabolic syndrome development by 23% (odds ratio [OR] 0.77; 0.62-0.96), and increased the chance to revert to a non-metabolic syndrome state by 32% (OR 1.32; 1.03-1.71). The metabolic syndrome is associated with a 1.5-fold increase in risk of vascular events in PAOD patients. Weight control reduces metabolic syndrome incidence and increases metabolic syndrome resolution during follow-up.