Medication underuse during long-term follow-up in patients with peripheral arterial disease.

BACKGROUND: Patients with peripheral arterial disease constitute a high-risk population. Guideline-recommended medical therapy use is therefore of utmost importance. The aims of our study were to establish the patterns of guideline-recommended medication use in patients with PAD at the time of vascular surgery and after 3 years of follow up, and to evaluate the effect of these therapies on long-term mortality in this patient group. METHODS AND RESULTS: Data on 711 consecutive patients with peripheral arterial disease undergoing vascular surgery were collected from 11 hospitals in the Netherlands (enrollment between May and December 2004). After 3.1+/-0.1 years of follow-up, information on medication use was obtained by a questionnaire (n=465; 84% response rate among survivors). Guideline-recommended medical therapy use for the combination of aspirin and statins in all patients and beta-blockers in patients with ischemic heart disease was 41% in the perioperative period. The use of perioperative evidence-based medication was associated with a reduction of 3-year mortality after adjustment for clinical characteristics (hazard ratio, 0.65; 95% CI, 0.45 to 0.94). After 3 years of follow-up, aspirin was used in 74%, statins in 69%, and beta-blockers in 54% of the patients respectively. Guideline-recommended medical therapy use for the combination of aspirin, statins, and beta-blockers was 50%. CONCLUSIONS: The use of guideline recommended therapies in the perioperative period was associated with reduction in long-term mortality in patients with peripheral arterial disease. However, the proportion of patients receiving these evidence-based treatments-both at baseline and 3 years after vascular surgery-was lower than expected based on the current guidelines. These data highlight a clear opportunity to improve the quality of care in this high-risk group of patients.

Fluvastatin and perioperative events in patients undergoing vascular surgery.

BACKGROUND: Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction. RESULTS: A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events. CONCLUSIONS: In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.)

Preoperative cardiac risk index predicts long-term mortality and health status.

OBJECTIVES: Peripheral arterial disease patients undergoing vascular surgery are known to be at risk for the occurrence of (late) cardiovascular events. Before surgery, the perioperative cardiac risk is commonly assessed using the Lee Risk Index score, a combination of 6 cardiac risk factors. This study assessed the predictive value of the Lee Risk Index for late mortality and long-term health status in patients after vascular surgery. METHODS: Between May and December 2004, data on 711 consecutive peripheral arterial disease patients undergoing vascular surgery were collected from 11 hospitals in the Netherlands. Before surgery, the Lee Risk Index was assessed in all patients. At 3-year follow-up, 149 patients died (21%) and the disease-specific Peripheral Artery Questionnaire (PAQ) was completed in 84% (n=465) of the survivors. Impaired health status according to the PAQ was defined by the lowest tertile of the PAQ summary score. Multivariable regression analyses were performed to investigate the prognostic ability of the Lee Index for mortality and impaired health status at 3-year follow-up. RESULTS: The Lee Risk Index proved to be an independent prognostic factor for both late mortality (1 risk factor hazard ratio (HR)=2.1; 95% confidence interval [CI], 1.2-3.6; 2 risk factors HR=2.4; 95% CI, 1.4-4.0 and >or=3 risk factors HR=3.2; 95% CI, 1.7-6.2) and impaired health status at 3-year follow-up (1 risk factor odds ratio [OR]=2.0; 95% CI, 1.1-3.5; 2 risk factors OR=2.9; 95% CI, 1.6-5.2 and >or=3 risk factors OR=3.2; 95% CI, 1.3-7.5). The predominant contributing factors associated with late mortality were cerebrovascular disease, insulin-dependent diabetes, and renal insufficiency. For impaired health status, ischemic heart disease, heart failure, cerebrovascular disease, insulin-dependent diabetes, and renal insufficiency were the prognostic factors. CONCLUSIONS: The preoperative Lee Risk Index is not only an important prognostic factor for in-hospital outcome but also for late mortality and impaired health status in patients with peripheral arterial disease.

Statin use in the elderly: results from a peripheral vascular survey in The Netherlands.

BACKGROUND: The prevalence of death due to cardiovascular disease increases steeply in vascular surgery patients with increasing age. Observational data in coronary heart disease and heart failure patients suggest that elderly patients are less optimally treated compared to younger patients. The aim of this study was to examine the differences in clinical characteristics and medical therapy of the elderly compared to younger patients in vascular surgery. Furthermore, we assessed the effect of statins on 1-year mortality in an unselected patient population. METHODS: Data on 711 consecutive peripheral vascular surgery patients were collected from 11 hospitals in The Netherlands in 2004. Elderly patients were defined as patients with an age above 70 years. Multivariable logistic regression analysis was used to identify clinical characteristics and medical therapy associated with older age. The effect of statins on 1-year mortality was assessed with Cox proportional hazard regression analysis. RESULTS: The mean age was 67 +/- 10 years and 299 (42%) patients were older than 70 years of age. Elderly patients showed a significant higher cardiac risk profile according to the Lee Cardiac Risk Index (Lee-Index) (>/=2 risk factors: 50% vs 32% in younger patients, P < .001). Multivariable analysis showed that older patients presented with a significant higher Lee-Index, a higher incidence of cardiac arrhythmias (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.1-3.3) and chronic obstructive pulmonary disease (COPD) (OR = 2.8; 95% CI = 1.7-4.7). However, smoking (OR = 0.5; 95% CI = 0.3-0.7) was less common in the elderly. Statins were significantly less often prescribed in the elderly (OR = 0.6; 95% CI = 0.4-0.8), although a beneficial effect of statins on 1-year mortality (HR = 0.3, 95% CI = 0.1-0.7) was observed. CONCLUSION: Elderly patients undergoing vascular surgery had a higher cardiac risk profile than younger patients. Despite this high cardiac risk and the beneficial effect, our study demonstrated that statins were less often used in elderly patients.

Guidelines for cardiac management in noncardiac surgery are poorly implemented in clinical practice: results from a peripheral vascular survey in the Netherlands.

BACKGROUND: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery recommend an algorithm for a stepwise approach to preoperative cardiac assessment in vascular surgery patients. The authors' main objective was to determine adherence to the ACC/AHA guidelines on perioperative care in daily clinical practice. METHODS: Between May and December 2004, data on 711 consecutive peripheral vascular surgery patients were collected from 11 hospitals in The Netherlands. This survey was conducted within the infrastructure of the Euro Heart Survey Programme. The authors retrospectively applied the ACC/AHA guideline algorithm to each patient in their data set and subsequently compared observed clinical practice data with these recommendations. RESULTS: Although 185 of the total 711 patients (26%) fulfilled the ACC/AHA guideline criteria to recommend preoperative noninvasive cardiac testing, clinicians had performed testing in only 38 of those cases (21%). Conversely, of the 526 patients for whom noninvasive testing was not recommended, guidelines were followed in 467 patients (89%). Overall, patients who had not been tested, irrespective of guideline recommendation, received less cardioprotective medications, whereas patients who underwent noninvasive testing were significantly more often treated with cardiovascular drugs (beta-blockers 43% vs. 77%, statins 52% vs. 83%, platelet inhibitors 80% vs. 85%, respectively; all P < 0.05). Moreover, the authors did not observe significant differences in cardiovascular medical therapy between patients with a normal test result and patients with an abnormal test result. CONCLUSION: This survey showed poor agreement between ACC/AHA guideline recommendations and daily clinical practice. Only one of each five patients underwent noninvasive testing when recommended. Furthermore, patients who had not undergone testing despite recommendations received as little cardiac management as the low-risk population.

Statins for the prevention of perioperative cardiovascular complications in vascular surgery.

Perioperative cardiovascular complications in vascular surgery remain a significant problem despite recent advancements in perioperative care. This clinical update summarizes the results of recent studies on the effectiveness and safety of perioperative statin use for the prevention of these perioperative cardiovascular complications. Five studies in patients undergoing major noncardiac vascular surgery and two studies in patients undergoing carotid endarterectomy are described. All studies reported a significant reduction in perioperative cardiovascular events in statin users compared with nonusers. The safety of perioperative statin use has not yet been fully elaborated, although current evidence suggests there is no extra risk from statin-induced side effects in the perioperative period.

Prognostic value of routine preoperative electrocardiography in patients undergoing noncardiac surgery.

Electrocardiography is commonly performed as part of preoperative cardiovascular risk assessment in patients undergoing noncardiac surgery. However, the prognostic value of such electrocardiography is still not clear. This study retrospectively studied 23,036 patients who underwent 28,457 surgical procedures at Erasmus Medical Center from 1991 to 2000. Patients were screened before surgery by type of surgery, cardiovascular risk factors (history of coronary heart disease, heart failure, diabetes mellitus, renal dysfunction, and stroke), and preoperative electrocardiography. Electrocardiographic (ECG) results showing atrial fibrillation, left or right bundle branch block, left ventricular hypertrophy, premature ventricular complexes, pacemaker rhythm, or Q-wave or ST-segment changes were classified as abnormal. Multivariate logistic regression was applied to evaluate the relation between ECG abnormalities and cardiovascular death. In-hospital cardiovascular death was observed in 199 of 28,457 patients (0.7%). Patients with abnormal ECG findings had a greater incidence of cardiovascular death than those with normal ECG results (1.8% vs 0.3%; adjusted odds ratio 4.5, 95% confidence interval 3.3 to 6.0). Adding ECG data to clinical risk factors and the type of surgery resulted in an improved C index for the prediction of cardiovascular death (0.79 vs 0.72). However, in patients who underwent low-risk or low- to intermediate-risk surgery, the absolute difference in the incidence of cardiovascular death between those with and without ECG abnormalities was only 0.5%. In conclusion, preoperative electrocardiography provides prognostic information in addition to clinical characteristics and the type of surgery. However, the usefulness of its routine use in lower risk surgery is questionable.

DSA versus multi-detector row CT angiography in peripheral arterial disease: randomized controlled trial.

PURPOSE: To prospectively compare therapeutic confidence in, patient outcomes (in terms of quality of life) after, and the costs of digital subtraction angiography (DSA) with those of multi-detector row computed tomographic (CT) angiography as the initial diagnostic imaging test in patients with peripheral arterial disease (PAD). MATERIALS AND METHODS: Institutional medical ethics committee approval and patient informed consent were obtained. Between April 2000 and August 2001, patients with PAD were randomly assigned to undergo either DSA or multi-detector row CT angiography as the initial diagnostic imaging test. Outcomes were the therapeutic confidence assessed by physicians (on a scale from 0 to 10), the need for additional imaging, the health-related quality of life at 6-month follow-up, diagnostic and therapeutic costs, and the costs for a hospital stay. Costs were computed from a hospital perspective according to Dutch guidelines for cost calculations in health care. Mean outcomes were compared between groups with unpaired t testing and were adjusted for predictive baseline characteristics with multivariable regression analysis. RESULTS: Among the 145 patients, 72 were randomly allocated to the DSA group and 73 to the CT angiography group. One patient in the DSA group had to be excluded. Mean age was 63 years in the DSA group and 64 years in the CT angiography group. There were 47 men in the DSA group and 58 men in the CT angiography group. Physician confidence in making a correct therapeutic choice was significantly higher at DSA (mean confidence score, 8.2) than at CT angiography (mean score, 7.2; P < .001). During 6-month follow-up, 14% less additional imaging was performed in the DSA group than in the CT angiography group (P = .3). No significant quality-of-life differences were found between groups. The diagnostic cost associated with DSA (564 +/- 210 euro [standard deviation]) was significantly higher than that associated with CT angiography (363 +/- 273 euro), a difference of -201 euro (95% confidence interval: -281 euro, -120 euro; P < .001). Therapeutic and hospitalization costs were similar for both strategies. CONCLUSION: These results suggest that use of noninvasive multi-detector row CT angiography instead of DSA as the initial diagnostic imaging test for PAD provides sufficient information for therapeutic decision making and reduces imaging costs.

Perioperative cardiovascular mortality in noncardiac surgery: validation of the Lee cardiac risk index.

PURPOSE: The Lee risk index was developed to predict major cardiac complications in noncardiac surgery. We retrospectively evaluated its ability to predict cardiovascular death in the large cohort of patients who recently underwent noncardiac surgery in our institution. METHODS: The administrative database of the Erasmus MC, Rotterdam, The Netherlands, contains information on 108 593 noncardiac surgical procedures performed from 1991 to 2000. The Lee index assigns 1 point to each of the following characteristics: high-risk surgery, ischemic heart disease, heart failure, cerebrovascular disease, renal insufficiency, and diabetes mellitus. We retrospectively used available information in our database to adapt the Lee index calculated the adapted index for each procedure, and analyzed its relation to cardiovascular death. RESULTS: A total of 1877 patients (1.7%) died perioperatively, including 543 (0.5%) classified as cardiovascular death. The cardiovascular death rates were 0.3% (255/75 352) for Lee Class 1, 0.7% (196/28 892) for Class 2, 1.7% (57/3380) for Class 3, and 3.6% (35/969) for Class 4. The corresponding odds ratios were 1 (reference), 2.0, 5.1, and 11.0, with no overlap for the 95% confidence interval of each class. The C statistic for the prediction of cardiovascular mortality using the Lee index was 0.63. If age and more detailed information regarding the type of surgery was retrospectively added, the C statistic in this exploratory analysis improved to 0.85. CONCLUSION: The adapted Lee index was predictive of cardiovascular mortality in our administrative database, but its simple classification of surgical procedures as high-risk versus not high-risk seems suboptimal. Nevertheless, if the goal is to compare outcomes across hospitals or regions using administrative data, the use of the adapted Lee index, as augmented by age and more detailed classification of type of surgery, is a promising option worthy of prospective testing.

Perioperative and long-term cardiovascular outcomes in patients undergoing endovascular treatment compared with open vascular surgery for abdominal aortic aneurysm or iliaco-femoro-popliteal bypass.

The aim of the present study was to determine the perioperative and long-term cardiac outcomes of patients who underwent elective open or endovascular major vascular surgery corrected for cardiac risk factors and dobutamine stress echocardiography. Consecutive patients who underwent either endovascular (n = 123) or open (n = 560) vascular surgery from 1996 to 2004 at Erasmus Medical Center were enrolled. Patients were screened for cardiac risk factors (advanced age, gender, angina pectoris, myocardial infarction, heart failure, diabetes, stroke, renal failure), cardioprotective medication, and the presence of stress-induced ischemia by dobutamine stress echocardiography. Postoperative data on troponin release and electrocardiography were routinely collected on days 1, 3, and 7 and before discharge. After discharge, patients were regularly screened at the outpatient clinic. The main outcome measures were perioperative and long-term cardiac death and myocardial infarction. The incidence of perioperative cardiac events was significantly less in endovascular-treated patients compared with conventionally treated patients, also after adjustment for clinical risk factors, dobutamine stress echocardiography, and medication (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.07 to 0.53). In contrast, during long-term follow-up (median 3.8 years, range 0 to 8.4), the incidence of long-term cardiac mortality and myocardial infarction were similar in the 2 groups (HR 0.89, 95% CI 0.52 to 1.52). In conclusion, endovascular stent grafting is associated with a reduced incidence of perioperative complications compared with open vascular surgery. Despite the initial perioperative survival benefit, patients who undergo endovascular surgery remain at high risk for late cardiac events.

Optimizing the prediction of perioperative mortality in vascular surgery by using a customized probability model.

BACKGROUND: Accurately assessing the probability of perioperative mortality can be useful in preoperative risk assessment and management. This study aimed to revise and customize the revised cardiac risk (Lee) index to estimate the probability of perioperative all-cause mortality in patients undergoing noncardiac vascular surgery. METHODS: We studied 2310 patients (mean age, 67.8 +/- 11.3 years; 1747 males) who underwent acute or elective major noncardiac vascular surgery between January 1, 1991, and December 31, 2000, at the Erasmus Medical Center, Rotterdam, the Netherlands. A total of 1537 patients were assigned for model development, in which the associations between predictor variables and mortality occurring within 30 days after surgery were identified to modify the Lee index, which was then evaluated in a validation cohort of 773 patients. RESULTS: The perioperative mortality rates were similar in the development (n = 103 [6.7%]) and validation (n = 50 [6.5%]) populations. The customized risk-prediction model for perioperative mortality identified type of vascular surgery, ischemic heart disease, congestive heart failure, previous stroke, hypertension, renal dysfunction, and chronic pulmonary disease as being associated with increased risk, whereas beta-blocker and statin use were associated with a lower risk of mortality. The performance of the customized index had excellent discriminative ability in both derivation and validation populations (concordance statistic, 0.88 and 0.85, respectively). CONCLUSIONS: The customized index provides more detailed information than the Lee index about the type of vascular procedure, clinical risk factors, and concomitant medication use. The customized probability model can be a useful tool to estimate the risk of perioperative all-cause mortality and facilitate subsequent treatment strategies.

Sac enlargement without endoleak: when and how to convert and technical considerations.

The primary goal of endovascular treatment of abdominal aortic aneurysms (AAA) is prevention of death from rupture. Even in the absence of an endoleak, the AAA may continue to enlarge. The pathogenesis of this phenomenon remains unclear. Therefore, surveillance after endovascular AAA treatment must include regular evaluation of aneurysm size, or even better, aneurysm volume. Aneurysm sac enlargement without an endoleak is not a benign condition. Recurrent or persistent pressurization of the AAA sac will eventually result in rupture. Besides that, continued expansion of the AAA sac can result in dilatation of the infrarenal neck and/or iliac arteries, which may threaten the integrity of proximal and distal anastomotic seals. Many centers will take a pragmatic approach in case of endotension and a growing AAA, and convert to open surgery with removal of the endograft and placement of a regular vascular graft. Direct puncture and pharmacological intervention in the cause of sac enlargement by local instillation seems logical, but has failed so far. The third option for aneurysm sac enlargement without an endoleak is laparoscopic or open fenestration of the aneurysm. Until permanent solutions for endotension and endoleaks are found, endovascular aneurysm repair will remain an imperfect long-term treatment and continued follow-up will be mandatory.

Peripheral arterial disease: therapeutic confidence of CT versus digital subtraction angiography and effects on additional imaging recommendations.

PURPOSE: To compare multi-detector row computed tomographic (CT) angiography and digital subtraction angiography (DSA) prior to revascularization in patients with symptomatic peripheral arterial disease for the purpose of assessing recommendations for additional imaging and physician confidence ratings for chosen therapy. MATERIALS AND METHODS: In a randomized controlled trial, 73 patients were assigned to CT angiography, and 72 were assigned to DSA. Physician confidence in the treatment decision was measured as a continuous outcome on a scale of 0-10 (uncertain to certain) and as a dichotomous outcome (further imaging recommended, yes or no). Mean confidence scores and additional imaging recommendations were compared between CT and DSA groups in an intention-to-diagnose-and-treat analysis. To detect trends in confidence, confidence scores were plotted over time, and multiple linear regression analysis was performed. To detect trends in additional imaging recommendations, logistic regression analysis was used. Data from eligible nonrandomized patients were analyzed separately. RESULTS: No statistically significant difference in baseline characteristics between randomized groups was found. CT had a lower confidence score than did DSA (7.2 vs 8.2, P < .001). Further imaging was recommended more often after CT (25 of 71 patients, 35%) than after DSA (nine of 66 patients, 14%; P = .003). Analysis of trends demonstrated increasing (but not statistically significant) confidence in CT and stable confidence in DSA. No significant difference was found in baseline characteristics between randomized and nonrandomized patients. Among nonrandomized patients, no significant difference in mean confidence score (8.2 vs 8.3, P = .26) was found between CT (n = 24) and DSA (n = 26). CONCLUSION: With CT angiography, physician confidence decreases with an associated increase in additional imaging prior to revascularization in patients with symptomatic peripheral arterial disease. Given that CT is less invasive than DSA, results suggest that CT may replace DSA in selected cases.

Comparison of catecholamine hormone release in patients undergoing carotid artery stenting or carotid endarterectomy.

PURPOSE: To investigate the pattern of catecholamine response in patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: Adrenaline, noradrenaline, and renin levels were measured at 5 time points in 12 patients undergoing 13 CEAs (1 bilateral) and 13 patients undergoing unilateral CAS. Arterial blood samples were taken at the following time points: (1) after induction in CEA patients or 5 minutes following first contrast injection in CAS patients, (2) 5 minutes following ICA clamp release in surgical patients or deflation of the balloon in the CAS cohort, (3) 60 minutes following ICA clamp release in surgical patients or deflation of the balloon in the CAS cohort, and (4) 24 hours following the procedure. Intraoperative blood pressure and heart rate were recorded using radial arterial monitoring. Changes in adrenaline, noradrenaline, and renin levels are expressed as ratios versus baseline. RESULTS: Patterns of adrenaline and noradrenaline release were significantly different in patients undergoing CAS and CEA, with much higher and more variable surges of adrenaline and noradrenaline occurring in CEA patients. Adrenaline and noradrenaline levels increased significantly over baseline following carotid artery clamping in patients undergoing CEA (noradrenaline ratio before clamping: 1.54+/-1.25, 24 hours after unclamping: 8.38+/-16.35 [p<0.001]; adrenaline ratio before clamping: 1.12+/-0.49, 60 minutes after unclamping: 17.59+/-19.14 [p<0.001]). Conversely, in patients undergoing CAS, catecholamine levels remained unchanged (noradrenaline ratio before dilation: 0.96+/-0.23, 24 hours after the procedure: 0.92+/-0.32 [p=NS]; adrenaline ratio before dilation: 0.83+/-0.33, 60 minutes after balloon deflation: 0.56+/-0.32 [p=NS]). CONCLUSIONS: CAS is associated with a significantly less marked catecholamine response than CEA, which may reflect down-regulation of the sympathetic nervous system in response to carotid sinus stimulation during carotid angioplasty.

Association between long-term statin use and mortality after successful abdominal aortic aneurysm surgery.

PURPOSE: To assess the potential long-term beneficial effects of statin use after successful abdominal aortic surgery. METHODS: Between 1991 and 2001, 570 patients underwent abdominal aortic aneurysm repair at the Erasmus Medical Center. Of the 519 patients (91%) who survived surgery beyond 30 days, 510 (98%) were followed for a median of 4.7 years (interquartile range, 2.7 to 7.3 years). These patients were evaluated for use of statins and beta-blockers, and for clinical risk factors (e.g., advanced age; prior myocardial infarction; diabetes mellitus; renal dysfunction; chronic pulmonary disease; history of heart failure, stroke, or angina), and their association with all-cause and cardiovascular mortality. RESULTS: A total of 205 patients (40%) died during follow-up; 140 due to cardiovascular causes. The incidence of all-cause (18% [27/154] vs. 50% [178/356], P <0.001) and cardiovascular (11% [17/154] vs. 34% [122/356], P <0.001) mortality was significantly lower in statin users than in nonstatin users. After adjusting for clinical risk factors and beta-blocker use, the association between statin use and reduced all-cause (hazard ratio [HR] = 0.4; 95% confidence interval [CI]: 0.3 to 0.6; P <0.001) and cardiovascular (HR = 0.3; 95% CI: 0.2 to 0.6; P <0.001) mortality persisted. Beta-blocker use was also associated with a significant reduction in all-cause (HR = 0.6; 95% CI: 0.5 to 0.9; P = 0.003) and cardiovascular (HR = 0.7; 95% CI: 0.4 to 0.9; P = 0.03) mortality. There was no evidence of an association between statin use and all-cause and cardiovascular mortality according to beta-blocker use or clinical risk factors. CONCLUSION: Long-term statin use is associated with reduced all-cause and cardiovascular mortality irrespective of clinical risk factors and beta-blocker use.

Photochemically modulated endothelial cell thrombogenicity via the thrombomodulin-tissue factor pathways.

Photodynamic therapy (PDT) is based on a photochemical reaction using a photosensitizer and light to produce reactive oxygen species that have biological effects. Although its application in some fields is largely based on thrombosis, in the vascular setting thrombosis must be prevented. In this study we examined the effects of PDT on the changes in activity of thrombomodulin (TM) and tissue factor (TF) as important regulators of the coagulation process of endothelial cells. Human umbilical vein endothelial cells were treated with PDT (chloro-aluminum-sulfonated phthalocyanine, lambda = 630 nm) at different light-energy doses, and TM and TF levels were measured using fluorescence spectroscopy. Microparticles (MP) were analyzed using flow cytometry analysis. PDT alters the thrombogenic state of endothelial cells by causing decreased expression of TM and increased expression of functional TF in a light-energy dose-dependent way. PDT-treated endothelial cells shed large numbers of MP containing high levels of TF. TF functionality of PDT-treated cells, measured by a Factor Xa-generating assay, was high. TF was located mostly intracellularly and in MP. The disturbed anticoagulant balance described in this study may explain the occurrence of thrombosis induced by PDT and, if not contained, dispute the suitability of PDT as an adjuvant modality to treat vascular restenosis.

Optimizing long-term cardiac management after major vascular surgery: Role of beta-blocker therapy, clinical characteristics, and dobutamine stress echocardiography to optimize long-term cardiac management after major vascular surgery.

BACKGROUND: Survivors of major vascular surgery are at increased risk of late cardiac complications. OBJECTIVE: To examine the cardioprotective effect of beta-blockers. METHODS: A follow-up study was conducted in 1286 patients who survived surgery for at least 30 days. Patients were screened for cardiac risk factors and dobutamine stress echocardiography (DSE) results; 1034 patients (80%) underwent preoperative DSE, and 370 (29%) received beta-blockers. The main outcome measure was late cardiac death or myocardial infarction. RESULTS: Seventy-four patients (5.8%) had late cardiac events. Cardiac event rates in patients with 0, 1 to 2, and 3 or more risk factors were 1.6%, 4.7%, and 19.2%, respectively. In patients without risk factors, beta-blockers were associated with improved event-free survival (2.8% vs 0%), and DSE had no additional prognostic value. In patients with 1 to 2 risk factors, the presence of ischemia during DSE increased cardiac events from 3.9% to 9.8%. However, if patients with ischemia were treated with beta-blockers, the risk decreased to 7.2%. In patients with 3 or more risk factors, DSE and beta-blockers stratified patients into intermediate- and high-risk groups. In patients without ischemia, beta-blockers reduced the cardiac event rate from 15.1% to 9.5%, whereas the cardioprotective effect was limited in patients with 3 or more risk factors and positive DSE findings. CONCLUSIONS: Long-term beta-blocker use is associated with a reduction in the cardiac event rate, except for patients with 3 or more risk factors and positive findings on DSE.