Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. METHODS: Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. RESULTS: 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2-11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01-1.46 and HR 1.26, 95% CI 1.10-1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. CONCLUSION: Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

The relation between healthy lifestyle changes and decrease in systemic inflammation in patients with stable cardiovascular disease.

BACKGROUND AND AIMS: Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease. METHODS: In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4-10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses. RESULTS: Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (ß-coefficient -0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (ß-coefficients -0.25; 95%CI -0.33,-0.16 and -0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (ß-coefficient -0.17; 95%CI -0.26,-0.07). CONCLUSIONS: Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.

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

AIM: To 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. METHODS: We 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. RESULTS: In 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)]. CONCLUSION: There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.

Relation between adiposity and vascular events, malignancy and mortality in patients with stable cerebrovascular disease.

BACKGROUND: Abdominal adiposity is associated with various risk factors including hypertension, and is therefore particularly relevant in patients with stable cerebrovascular disease (CeVD). A U-shaped relation between body mass index (BMI, kg m-2) and cardiovascular events is often described. Whether this U-shape persists for abdominal adiposity, and consequently which reference values should guide clinical practice, is unclear. We described the relation between multiple adiposity measurements and risk of vascular events, vascular mortality, malignancy and all-cause mortality in patients with clinically stable CeVD. METHODS: During a median follow-up time of 6.8 years, 1767 patients were prospectively followed. Relations were assessed using multivariable adjusted Cox proportional hazards models. Adiposity was assessed with BMI, waist circumference (stratified by gender) and the contribution of visceral fat to total abdominal fat (VAT%) measured using ultrasound. Relations were nonlinear if the χ2-statistic of the nonlinear term was significant (P-value<0.05). Nadirs were reported for nonlinear and hazard ratios (HRs) for linear relations. RESULTS: The relations between BMI and outcomes were nonlinear with nadirs ranging between 27.1 (95% confidence interval (CI) 21.9-29.3) kg m2 for vascular mortality and 28.1 (95% CI, 19.0-38.2)) kg m-2 for malignancy. The relation between waist circumference and all-cause mortality was nonlinear with a nadir of 84.0 (95% CI, 18.7-134.8) cm for females and 94.8 (95% CI, 80.3-100.1) cm for males. No nonlinearity was detected for VAT%. A 1-s.d. (9.8%) increase in VAT% was related to both vascular (HR, 1.23, 95% CI 1.00-1.51) and all-cause mortality (HR, 1.22, 95% CI 1.05-1.42). CONCLUSIONS: In patients with CeVD, a BMI around 27-28 kg m-2 relates to the lowest risk of vascular events, vascular mortality, malignancy and all-cause mortality. However, increasing abdominal adiposity confers a higher risk of all-cause mortality. Thus, whereas traditional BMI cutoffs may be re-evaluated in this population, striving for low abdominal obesity should remain a goal.

Individualized prediction of the effect of angiotensin receptor blockade on renal and cardiovascular outcomes in patients with diabetic nephropathy.

AIMS: To predict individualized treatment effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal complications in order to help clinicians and patients assess the benefit of treatment (or adherence) and estimate remaining disease risk. MATERIALS AND METHODS: In patients with diabetic nephropathy, the 3-year treatment effect of ARBs was predicted in terms of absolute risk reduction (ARR) for end-stage renal disease (ESRD) and cardiovascular disease (CVD; i.e. myocardial infarction, stroke, hospitalization for heart failure) and all-cause mortality. Competing-risk-adjusted proportional hazard models were developed based on the Irbesartan Diabetic Nephropathy Trial (IDNT) and externally validated in the Reduction of Endpoints NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. RESULTS: Predictors included in the model were age, sex, smoking sex, systolic blood pressure, urinary albumin/creatinine ratio, estimated glomerular filtration rate, albumin and phosphorus. The median predicted 3-year risk without treatment was 6.0% for ESRD and 28.0% for CVD and mortality. The median [interquartile range (IQR)] predicted 3-year ARR was 1.2 (0.4-3.1)% for ESRD and 2.2 (1.8-2.6)% for CVD and mortality, resulting in a combined ARR of 3.4 (2.4-5.5)%. The remaining disease risk was 4.7 (IQR 1.7-12.8)% for ESRD and 25.8% (IQR 20.3-31.9)% for CVD and mortality. CONCLUSIONS: The combined effects of ARBs on ESRD and CVD and mortality in patients with diabetic nephropathy vary considerably between patients. A substantial proportion of patients remain at high risk for both outcomes despite ARB treatment.

Pemetrexed plus carboplatin versus pemetrexed in pretreated patients with advanced non-squamous non-small-cell lung cancer: treating the right patients based on individualized treatment effect prediction.

BACKGROUND: Translating results from randomized clinical trials (RCTs) to individual patients in clinical practice is challenging, as treatment effects can vary substantially among individuals. Data from RCTs can be used for individualized treatment effect prediction, to identify patients who benefit from specific treatments. In this study, we developed and validated a prediction model for estimating absolute treatment effect of pemetrexed plus carboplatin versus single-agent pemetrexed in the second-line treatment of non-squamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Using data of relapsed patients with advanced non-squamous NSCLC from the NVALT-7 trial, a Weibull model for prediction of gain in median progression-free survival (PFS) by pemetrexed-carboplatin was derived based on patient and tumor characteristics. The model was externally validated in the GOIRC 02-2006 trial. The applicability of the model for guiding clinical decision-making was evaluated using decision curve analysis. RESULTS: A wide distribution of predicted gain in median PFS by pemetrexed-carboplatin over pemetrexed was found, with a median of 0.7 months (interquartile range: -0.1 to 1.5 months). Patients who benefited most included women, those with stage IV, high body mass index and/or adenocarcinoma. External validation showed satisfactory calibration and moderate discrimination (C-index: 0.61, 95% confidence interval 0.56-0.67). Decision curve analysis confirmed that the model adequately identified patients who benefit from pemetrexed-carboplatin, as prediction-based treatment led to improvement in net benefit with regard to PFS and overall survival when assuming a treatment threshold of 0-5 months gain in PFS, compared with other treatment strategies. CONCLUSIONS: The effects of pemetrexed-carboplatin can be predicted for individual patients based on routinely available patient and tumor characteristics. There is important heterogeneity in the effects on PFS of pemetrexed-carboplatin versus pemetrexed in pretreated patients with advanced non-squamous NSCLC. Individualized prediction of treatment effect could be used to guide shared decision-making by discriminating patients who benefit most, to improve clinical outcome. CLINICAL TRIAL NUMBERS: NVALT-7: ISRCTN38269072 (ISRCTN registry), GOIRC 02-2006: NCT00786331 (clinicaltrials.gov).

Risk Chart for Future Mortality and Ischaemic Events Following Peripheral Bypass Surgery.

OBJECTIVES: A prediction model to identify determinants and quantify the risk of future ischaemic events in patients with peripheral arterial disease (PAD) provides a personal risk profile to offer individualized patient care. A risk chart was derived and validated in patients who received infrainguinal bypass surgery. METHODS: The Bypass Oral anticoagulants or Aspirin Risk Chart (BOA-RC2) was based on a pre-defined subgroup of the Dutch BOA trial (N = 482), the derivation cohort. The primary outcome event for BOA-RC2 was the composite of all cause death, non-fatal myocardial infarction, or non-fatal ischaemic stroke during a 10 year follow up. Determinants and long-term risk were identified with multivariate Cox regression analyses. Validation of the BOA-RC2 was performed in the remaining patients of the complete BOA trial cohort (N = 2,650 - 482 = 2,168), the validation cohort. RESULTS: The primary outcome event occurred in 67% (321/454) of the derivation cohort and in 66% (1,371/2,083) of the validation cohort during a median follow up of 6.6 years. The BOA-RC2 included the following determinants: age, critical limb ischaemia, diabetes, and a prior vascular intervention. The performance of the BOA-RC2 was good with a Brier score of 0.19, an area under the curve of 0.73, and a Hosmer-Lemeshow statistic of p = .9. CONCLUSIONS: The BOA-RC2 proves to be fit for the prediction of mortality and major ischaemic events in patients after peripheral bypass surgery. The BOA-RC2 can be used to adequately inform the patient about his/her risk of future events in an illustrative manner and stress the necessity of preventative measures, such as lifestyle adjustments, screening for risk factors, and drug treatments. In the future, the BOA-RC2 may be of interest to identify patients at high risk of mortality and ischaemic events for clinical research on new therapeutic options.

Osteoporosis markers on low-dose lung cancer screening chest computed tomography scans predict all-cause mortality.

OBJECTIVES: Further survival benefits may be gained from low-dose chest computed tomography (CT) by assessing vertebral fractures and bone density. We sought to assess the association between CT-measured vertebral fractures and bone density with all-cause mortality in lung cancer screening participants. METHODS: Following a case-cohort design, lung cancer screening trial participants (N = 3,673) who died (N = 196) during a median follow-up of 6 years (inter-quartile range: 5.7-6.3) were identified and added to a random sample of N = 383 from the trial. We assessed vertebral fractures using Genant's semiquantative method on sagittal reconstructions and measured bone density (Hounsfield Units (HU)) in vertebrae. Cox proportional hazards modelling was used to determine if vertebral fractures or bone density were independently predictive of mortality. RESULTS: The prevalence of vertebral fractures was 35% (95% confidence interval 30-40%) among survivors and 51% (44-58%) amongst cases. After adjusting for age, gender, smoking status, pack years smoked, coronary and aortic calcium volume and pulmonary emphysema, the adjusted hazard ratio (HR) for vertebral fracture was 2.04 (1.43-2.92). For each 10 HU decline in trabecular bone density, the adjusted HR was 1.08 (1.02-1.15). CONCLUSIONS: Vertebral fractures and bone density are independently associated with all-cause mortality. KEY POINTS: • Lung cancer screening chest computed tomography contains additional, potentially useful information. • Vertebral fractures and bone density are independently predictive of mortality. • This finding has implications for screening and management decisions.

The Dutch hospital standardised mortality ratio (HSMR) method and cardiac surgery: benchmarking in a national cohort using hospital administration data versus a clinical database.

OBJECTIVE: To compare the accuracy of data from hospital administration databases and a national clinical cardiac surgery database and to compare the performance of the Dutch hospital standardised mortality ratio (HSMR) method and the logistic European System for Cardiac Operative Risk Evaluation, for the purpose of benchmarking of mortality across hospitals. METHODS: Information on all patients undergoing cardiac surgery between 1 January 2007 and 31 December 2010 in 10 centres was extracted from The Netherlands Association for Cardio-Thoracic Surgery database and the Hospital Discharge Registry. The number of cardiac surgery interventions was compared between both databases. The European System for Cardiac Operative Risk Evaluation and hospital standardised mortality ratio models were updated in the study population and compared using the C-statistic, calibration plots and the Brier-score. RESULTS: The number of cardiac surgery interventions performed could not be assessed using the administrative database as the intervention code was incorrect in 1.4-26.3%, depending on the type of intervention. In 7.3% no intervention code was registered. The updated administrative model was inferior to the updated clinical model with respect to discrimination (c-statistic of 0.77 vs 0.85, p<0.001) and calibration (Brier Score of 2.8% vs 2.6%, p<0.001, maximum score 3.0%). Two average performing hospitals according to the clinical model became outliers when benchmarking was performed using the administrative model. CONCLUSIONS: In cardiac surgery, administrative data are less suitable than clinical data for the purpose of benchmarking. The use of either administrative or clinical risk-adjustment models can affect the outlier status of hospitals. Risk-adjustment models including procedure-specific clinical risk factors are recommended.

Internet based vascular risk factor management for patients with clinically manifest vascular disease: randomised controlled trial.

OBJECTIVE: To investigate whether an internet based, nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinically manifest vascular disease. DESIGN: Prospective randomised controlled trial. SETTING: Multicentre trial in secondary and tertiary healthcare setting. PARTICIPANTS: 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with at least two treatable risk factors not at goal. INTERVENTION: Personalised website with an overview and actual status of patients' risk factors and mail communication via the website with a nurse practitioner for 12 months; the intervention combined self management support, monitoring of disease control, and drug treatment. MAIN OUTCOME MEASURES: The primary endpoint was the relative change in Framingham heart risk score after 1 year. Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor. RESULTS: Participants' mean age was 59.9 (SD 8.4) years, and most patients (n=246; 75%) were male. After 1 year, the relative change in Framingham heart risk score of the intervention group compared with the usual care group was -14% (95% confidence interval -25% to -2%). At baseline, the Framingham heart risk score was higher in the intervention group than in the usual care group (16.1 (SD 10.6) v 14.0 (10.5)), so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score. This produced a relative change of -12% (-22% to -3%) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and -8% (-18% to 2%) adjusted for the baseline score. Of the individual risk factors, a difference between groups was observed in low density lipoprotein cholesterol (-0.3, -0.5 to -0.1, mmol/L) and smoking (-7.7%, -14.9% to -0.4%). Some other risk factors tended to improve (body mass index, triglycerides, systolic blood pressure, renal function) or tended to worsen (glucose concentration, albuminuria). CONCLUSION: An internet based, nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease. TRIAL REGISTRATION: Clinical trials NCT00785031.

Effectiveness of a hospital-based vascular screening programme (SMART) for risk factor management in patients with established vascular disease or type 2 diabetes: a parallel-group comparative study.

AIMS: Modification of vascular risk factors is effective in reducing mortality and morbidity in patients with symptomatic atherosclerosis; however, it is difficult to achieve and maintain. The aim of the Risk management in Utrecht and Leiden Evaluation (RULE) study was to assess risk factor status after referral in patients with established vascular disease or type 2 diabetes who took part in the multidisciplinary hospital-based vascular screening programme, Second Manifestations of ARTerial disease, compared with a group who did not participate in such a programme. METHODS AND RESULTS: Patients with type 2 diabetes, coronary artery disease, cerebrovascular disease or peripheral arterial disease referred by general practitioners to the medical specialist at the University Medical Center (UMC) Utrecht (a setting with a vascular screening programme of systematic screening of risk factors followed by treatment advice) and the Leiden UMC (a setting without such a screening programme), were enrolled in the study. Blood pressure, levels of lipids, glucose and creatinine, weight, waist circumference and smoking status were measured in patients 12-18 months after referral to the two hospitals. A total of 604 patients were treated in the setting with a vascular screening programme and 566 in the setting without such a programme; 70% of all patients were male, with a mean age of 61 +/- 10 years. Amongst screened patients, systolic blood pressure [2.5 mmHg, 95% confidence interval (CI) 0.3-4.6] and the level of LDL cholesterol (0.3 mmol L(-1), 95% CI 0.2-0.4) were lower compared with the group that received usual care, after a median of 16 months from referral. CONCLUSION: Systematic screening of risk factors, followed by evidence-based, tailored treatment advice contributed to slightly better risk factor reduction in patients with established vascular disease or type 2 diabetes. However, a large proportion of patients did not reach the treatment goals according to (inter)national guidelines. Systematic screening of vascular risk factors alone is not enough for adequate risk factor management in high-risk patients.

Leisure-time physical activity and risk of type 2 diabetes in patients with established vascular disease or poorly controlled vascular risk factors.

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.

Low plasma HDL-c, a vascular risk factor in high risk patients independent of LDL-c.

BACKGROUND: High concentrations of high density lipoprotein-cholesterol (HDL-c) are associated with lower cardiovascular risk, but it is not known whether this is also the case in the presence of intensive low density lipoprotein-cholesterol (LDL-C) therapy. In this study, we determined the relationship between HDL-c and new non-fatal or fatal vascular events in patients with various manifestations of clinical evident vascular disease and evaluated whether this relationship is modified by LDL-c levels. MATERIALS AND METHODS: Prospective single centre, cohort study of 3837 patients with a history or recent diagnosis of clinical manifest vascular disease (coronary, cerebrovascular, peripheral arterial disease or abdominal aortic aneurysm) The relationship between HDL-c quintiles and time to a new event (myocardial infarction, ischaemic stroke, vascular death) was quantified with Cox-regression models and adjusted for potential confounders (age, gender, body mass index, type 2 diabetes, triglycerides, smoking, use of alcohol and lipid-lowering therapy). Effect modification of LDL-c was assessed with interaction terms. RESULTS: During a median follow up of 3.3 (range 0.1-9.5) years, a total of 465 first new events occurred. Compared with the lowest quintile, the upper quintile of HDL-c levels was associated with a lower risk for new events; Hazard Ratio 0.61 (95% CI 0.43-0.86) irrespective of the localisation of vascular disease and use of lipid-lowering medication. Higher HDL-c levels were associated with comparably lower risks for vascular events in patients with LDL-c levels above and below 2.5 mmol L(-1) (P-values for interaction > 0.05). CONCLUSIONS: Patients with various clinical manifestations of vascular diseases in the highest HDL-c quintile have a lower risk for vascular events compared with patients in the lowest HDL-c quintile. Further, the current results expand the evidence by showing that also in a cohort of patients with various localisations of clinical evident vascular disease, in which statins were widely used, higher HDL-c levels confer a lower risk for developing new vascular events, irrespective of the localisation of vascular disease, use of lipid-lowering medication and plasma LDL-c concentration.

Unrecognised myocardial infarction in subjects at high vascular risk: prevalence and determinants.

OBJECTIVE: To investigate the prevalence and determinants of unrecognised myocardial infarction (UMI). DESIGN, SETTING, PATIENTS: In this cross-sectional study in a tertiary centre, a delayed enhancement cardiac MRI (DE-CMR), which identifies both Q-wave and non-Q wave MIs, was performed in 502 subjects with manifest extracardiac atherosclerotic disease or marked risk factors for atherosclerosis without symptomatic coronary artery disease. MAIN OUTCOME MEASURES: UMI was defined as the presence of delayed enhancement without corresponding clinical history. RESULTS: DE-CMR was of sufficient image quality in 480 (95.6%) subjects. A UMI was present in 45 (9.4%) of all subjects; in 13.1% of men and in 3.7% of women. The risk of UMI increased from 6.0% (95% CI 2.2 to 9.8%) in those with two vascular risk factors up to 26.2% (95% CI 15.2 to 37.3%) in those with four or five risk factors. In a multivariable analysis, the risk of UMI was related to male gender (OR 2.3 (95% CI 1.0 to 5.6)), age (OR 1.04 (95% CI 1.00 to 1.07) per year), ever smoking (OR 3.1 (95% CI 1.0 to 9.1), history of stroke (OR 1.9 (95% CI 0.8 to 4.3)) and history of aneurysm of the abdominal aorta (OR 2.6 (95% CI 1.0 to 6.9)). CONCLUSIONS: In cardiac asymptomatic subjects at high vascular risk, UMI is common. The risk of UMI increases with increasing presence of risk factors.

[Echographic screening of the abdominal aorta in older men is not useful]. / Echografische screening van de aorta abdominalis bij oudere mannen is niet zinvol.

Aneurysm of the abdominal aorta (AAA) is a normal symptom of old age, the prevalence and chance of rupture of which are highly exaggerated, and which very seldom leads to death. The result of screening is that many men (5%) are medicalised unjustly and exposed to the severe risks of a surgical intervention. The mortality during open surgery is 5-6%. Screening has no effect on the total mortality.

Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study.

PURPOSE: To prospectively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures (VCF) treated with percutaneous vertebroplasty (PV) compared with optimal pain medication (OPM). METHODS: Randomization of patients in 2 groups: treatment by PV or OPM. After 2 weeks, patients from the OPM arm could change therapy to PV. Patients were evaluated 1 day and 2 weeks after treatment. Visual analog score (VAS) for pain and analgesic use were assessed before, and 1 day and 2 weeks after start of treatment. Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and Roland-Morris Disability (RMD) questionnaire scores were assessed before and 2 weeks after start of treatment. Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period. RESULTS: Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment. Two weeks after treatment, the mean VAS was less but not significantly different in patients treated with OPM, whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores. Scores in the PV arm were influenced by occurrence of new VCF in 2 patients. After 2 weeks OPM, 14 patients requested PV treatment. All scores, 1 day and 2 weeks after PV, were significantly better compared with scores during conservative treatment. CONCLUSION: Pain relief and improvement of mobility, function, and stature after PV is immediate and significantly better in the short term compared with OPM treatment.

Breast arterial calcifications are correlated with subsequent development of coronary artery calcifications, but their aetiology is predominantly different.

OBJECTIVE: To study whether calcifications in breast arteries, as seen on mammograms, predict future development of coronary artery calcifications. METHODS: We studied 499 women, aged 49-70 years, participating in a breast cancer screening program and investigated whether arterial calcifications in the breast (BAC) are associated with coronary arterial calcifications (CAC) after 9 years follow-up. Mammograms were reviewed for the presence of BAC. CAC was assessed by multi slice computed tomography (MSCT). With logistic regression analysis the independent effect of various risk factors on BAC and CAC was measured. RESULTS: BAC was present in 58 of 499 women (12%) and CAC score>0 was present in 262 of 499 women (53%). BAC was strongly associated with CAC (OR 3.2, 95% CI 1.71-6.04) and this remained significant after adjustment for age at baseline and the duration of follow-up (OR 2.1, 95% CI 1.10-4.23). Most CV risk factors were associated with CAC but not with BAC. Only parity was significantly associated with both increased CAC (OR 2.1, 95% CI 1.21-3.60) and increased BAC (OR 5.3, 95% CI 1.23-22.43). Breastfeeding was associated with BAC (OR 3.4, 95% CI 1.40-8.23) but not with CAC (OR 1.3, 95% CI 0.84-1.93). CONCLUSION: Breast arterial calcifications are predictive of subsequent development of calcifications in the coronary arteries.

Coronary collaterals--insights in molecular determinants and prognostic relevance.

In the field of molecular cardiology, recently several determinants of coronary collateral circulation have been identified. Knowing these factors may aid risk-stratification and put forward targets for intervention by stimulating development of collateral blood vessels (arteriogenesis). However, prognostic importance of coronary collaterals is not yet beyond debate, and seems to be modified by the extent of atherosclerotic burden. Combining these insights is essential to increase our understanding of these mechanisms and to proceed with developing strategies for risk-stratification and therapeutic stimulation of arteriogenesis.

Pain response in the first trimester after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures with or without bone marrow edema.

BACKGROUND AND PURPOSE: Presence of bone marrow edema (BME) in osteoporotic vertebral compression fractures (VCF) detected by MR imaging as selection criterion for percutaneous vertebroplasty (PV) is speculative. To clarify significance of BME in VCF, we assessed pain response after PV in patients with VCF with full BME versus patients with VCF with absent BME. METHODS: From a cohort of patients with painful VCF selected for PV, pain response in 14 patients with absent BME in VCF was prospectively compared with pain response in 31 patients with full BME in VCF. Pain was evaluated before PV and at 1 and 3 months after PV with visual analog scores and analgesics used. Back pain in general and at treated vertebral levels was assessed. RESULTS: Pain decrease after PV at treated levels was observed in 10 (71%) patients with absent BME in VCF at both follow-up periods and in 29 (94%) patients with full BME 1 month after PV and 30 (97%) at 3 months after PV. Differences between the groups were significant (P = .04 at 1 month; P = .01 at 3 months). Pain response was not affected by other patient or imaging characteristics. General back pain after PV was comparable in both groups after PV (P = .08 at 1 month; P = .4 at 3 months). CONCLUSION: Pain decrease after PV in patients with VCF is more frequently observed when full BME is present. Because 71% of patients with VCF with absent BME responded favorably on pain, PV should not be withheld based on absence of BME alone.