Gijs M.J.M. Welten

Long-Term Prognosis of Patients With Peripheral Arterial Disease: A Comparison in Patients With Coronary Artery Disease

OBJECTIVES This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. BACKGROUND The PAD is considered to be a risk factor for adverse late outcome. METHODS A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. RESULTS The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. CONCLUSIONS Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

Impact of Cardioselective β-Blockers on Mortality in Patients with Chronic Obstructive Pulmonary Disease and Atherosclerosis

RATIONALE beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms. OBJECTIVES We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery. METHODS We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose. MEASUREMENTS AND MAIN RESULTS There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not. CONCLUSIONS Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.

Clinical ResearchPeripheral Vascular DiseaseLong-Term Prognosis of Patients With Peripheral Arterial Disease: A Comparison in Patients With Coronary Artery Disease

OBJECTIVES This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. BACKGROUND The PAD is considered to be a risk factor for adverse late outcome. METHODS A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. RESULTS The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. CONCLUSIONS Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

Effect of Statin Therapy on Mortality in Patients With Peripheral Arterial Disease and Comparison of Those With Versus Without Associated Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) and peripheral arterial disease (PAD) are both inflammatory conditions. Statins are commonly used in patients with PAD and have anti-inflammatory properties, which may have beneficial effects in patients with COPD. The relation between statin use and mortality was investigated in patients with PAD with and without COPD. From 1990 to 2006, we studied 3,371 vascular surgery patients. Statin use was noted at baseline and, if prescribed, converted to <25% (low dose) and > or =25% (intensified dose) of the maximum recommended therapeutic dose. The diagnosis of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease guidelines using pulmonary function test. End points were short- (30-day) and long-term (10-year) mortality. A total of 330 patients with COPD (25%) used statins, and 480 patients (23%) without COPD. Statin use was independently associated with improved short- and long-term survival in patients with COPD (odds ratio 0.48, 95% confidence interval [CI] 0.23 to 1.00; hazard ratio 0.67, 95% CI 0.52 to 0.86, respectively). In patients without COPD, statins were also associated with improved short- and long-term survival (odds ratio 0.42, 95% CI 0.20 to 0.87; hazard ratio 0.76, 95% CI 0.60 to 0.95, respectively). In patients with COPD, only an intensified dose of statins was associated with improved short-term survival. However, for the long term, both low-dose and intensive statin therapy were beneficial. In conclusion, statin use was associated with improved short- and long-term survival in patients with PAD with and without COPD. Patients with COPD should be treated with an intensified dose of statins to achieve an optimal effect on both the short and long term.

Renal Insufficiency and Mortality in Patients with Known or Suspected Coronary Artery Disease

It remains unclear whether mild renal dysfunction is associated with adverse cardiovascular outcome. We investigated whether estimated glomerular filtration rate (eGFR) was associated with mortality and cardiac death among 6447 patients with known or suspected coronary artery disease over a mean follow-up of 7 yr. Cumulative 5- and 10-yr survival rates decreased in a graded fashion from 88% and 70%, respectively, for those with normal renal function to 43% and 33% for those with eGFR <30 ml/min. Compared with patients with normal renal function, the multivariable adjusted hazard ratios for all-cause mortality among patients with mild, moderate, and severe renal impairment were 1.33 (95% confidence interval [CI], 1.21-1.48), 1.67 (95% CI, 1.44-1.93), and 3.38 (95% CI, 2.73-4.19), respectively. Similar relationships between cardiac death and decreasing renal function were found. In conclusion, renal function is a graded and independent predictor of long-term mortality in patients with known or suspected coronary artery disease. Intense treatment and close surveillance of these patients is encouraged.

Statin use is associated with early recovery of kidney injury after vascular surgery and improved long-term outcome

BACKGROUND Acute kidney injury (AKI) after major vascular surgery is an important risk factor for adverse long-term outcomes. The pleiotropic effects of statins may reduce kidney injury caused by perioperative episodes of hypotension and/or suprarenal clamping and improve long-term outcomes. METHODS Of 2170 consecutive patients undergoing lower extremity bypass or abdominal aortic surgery from 1995 to 2006, cardiac risk factors and medication were noted. A total of 515/1944 (27%) patients were statin users. Creatinine clearance (CrCl) was assessed preoperatively at 1, 2 and 3 days after surgery. Outcome measures were postoperative AKI and long-term mortality. Postoperative kidney injury was defined as a >10% decrease in CrCl on Day 1 or 2, compared to the baseline. Recovery of kidney function was defined as a CrCl >90% of the baseline value at Day 3 after surgery. Multivariable Cox regression analysis, including baseline cardiovascular risk factors, baseline CrCl and propensity score for statin use, was applied to evaluate the influence of statins on early postoperative kidney injury and long-term survival. RESULTS AKI occurred in 664 (34%) patients [median -25% CrCl, range (-10% to -71%)]. Of these 664 patients, 313 (47%) had a complete recovery of kidney function at Day 3 after surgery. Age, hypertension, suprarenal cross-clamping and baseline CrCl predicted the development of kidney injury during the postoperative period. The incidence of kidney injury was similar among statin users and non-users (29% versus 25%, OR 1.15, 95% CI 0.9-1.5). However, if kidney function deteriorated, statin use was associated with increased odds of complete kidney function recovery (OR 2.0, 95% CI 1.0-3.8). During a mean follow-up of 6.24 years, half of the patients died (55%). Importantly, statin use was also associated with an improved long-term survival, irrespective of kidney function change (HR 0.60, 95% CI 0.48-0.75). CONCLUSION Statin use is associated with improved recovery from AKI after major surgery and has a beneficial effect on long-term survival.

Anemia as an Independent Predictor of Perioperative and Long-Term Cardiovascular Outcome in Patients Scheduled for Elective Vascular Surgery

Anemia is common in patients scheduled for vascular surgery and is a risk factor for adverse cardiac outcome. However, it is unclear whether this is an independent risk factor or an expression of underlying co-morbidities. In total, 1,211 patients (77% men, 68 +/- 11 years of age) were enrolled. Anemia was defined as serum hemoglobin levels <13 g/dl for men and <12 g/dl for women and was divided into tertiles to compare mild (men 12.2 to 13.0, women 11.2 to 12.0), moderate (men 11.0 to 12.1, women 10.2 to 11.1), and severe (men 7.2 to 11.0, women 7.5 to 10.1) anemia with nonanemia. Outcome measurements were 30-day and 5-year major adverse cardiac events (MACEs; cardiac death or myocardial infarction). All risk factors were noted. Multivariable logistic and Cox regression analyses were used, adjusting for all cardiac risk factors, including heart failure and renal disease. Data are presented as hazard ratios with 95% confidence intervals. In total, 74 patients (6%) had 30-day MACEs and 199 (17%) had 5-year MACEs. Anemia was present in 399 patients (33%), 133 of whom had mild anemia, 133 had moderate anemia, and 133 had severe anemia. Presence of anemia was associated with renal dysfunction, diabetes, and heart failure. After adjustment for all clinical risk factors, 30-day hazard ratios for a MACE per anemia group were 1.8 for mild (0.8 to 4.1), 2.3 for moderate (1.1 to 5.4), and 4.7 for severe (2.6 to 10.9) anemia, and 5-year hazard ratios for MACE per anemia group were 2.4 for mild (1.5 to 4.2), 3.6 for moderate (2.4 to 5.6), and 6.1 for severe (4.1 to 9.1) anemia. In conclusion, the presence and severity of preoperative anemia in vascular patients are significant predictors of 30-day and 5-year cardiac events, regardless of underlying heart failure or renal disease.

Preoperative Estimates of Glomerular Filtration Rate as Predictors of Outcome after Surgery: A Systematic Review and Meta-analysis

Background:Kidney dysfunction is a strong determinant of prognosis in many settings. Methods:A systematic review and meta-analysis was undertaken to explore the relationship between estimated glomerular filtration rate (eGFR) and adverse outcomes after surgery. Cohort studies reporting the relationship between eGFR and major outcomes, including all-cause mortality, major adverse cardiovascular events, and acute kidney injury after cardiac or noncardiac surgery, were included. Results:Forty-six studies were included, of which 44 focused exclusively on cardiac and vascular surgery. Within 30 days of surgery, eGFR less than 60 ml·min·1.73 m−2 was associated with a threefold increased risk of death (multivariable adjusted relative risk [RR] 2.98; 95% confidence interval [CI] 1.95–4.96) and acute kidney injury (adjusted RR 3.13; 95% CI 2.22–4.41). An eGFR less than 60 ml·min·1.73 m−2 was associated with an increased risk of all-cause mortality (adjusted RR 1.61; 95% CI 1.38–1.87) and major adverse cardiovascular events (adjusted RR 1.49; 95% CI 1.32–1.67) during long-term follow-up. There was a nonlinear association between eGFR and the risk of early mortality such that, compared with patients having an eGFR more than 90 ml·min·1.73 m−2 the pooled RR for death at 30 days in those with an eGFR between 30 and 60 ml·min·1.73 m−2 was 1.62 (95% CI 1.43–1.80), rising to 2.85 (95% CI 2.49–3.27) in patients with an eGFR less than 30 ml·min·1.73 m−2 and 3.75 (95% CI 3.44–4.08) in those with an eGFR less than 15 ml·min·1.73 m−2. Conclusion:There is a powerful relationship between eGFR, and both short- and long-term prognosis after, predominantly cardiac and vascular, surgery.

Long-term prognosis of patients with peripheral arterial disease with or without polyvascular atherosclerotic disease

AIMS Patients with peripheral atherosclerotic disease often have multiple affected vascular beds (AVB), however, data on long-term follow-up and medical therapy are scarce. We assessed the prevalence and prognostic implications of polyvascular disease on long-term outcome in symptomatic peripheral arterial disease (PAD) patients. METHODS AND RESULTS Two thousand nine hundred and thirty-three consecutive patients were screened prior to surgery for concomitant documented cerebrovascular disease and coronary artery disease. The number of AVB was determined. Cardiovascular medication as recommended by guidelines was noted at discharge. Single, two, and three AVB were detected in 1369 (46%), 1249 (43%), and 315 (11%) patients, respectively. During a median follow-up of 6 years, 1398 (48%) patients died, of which 54% secondary to cardiovascular cause. After adjustment for baseline cardiac risk factors and discharge-medication, the presence of 2-AVB or 3-AVB was associated with all-cause mortality (HR 1.3 95% CI 1.2-1.5; HR 1.8 95% CI 1.5-2.2) and cardiovascular mortality (HR 1.5 95% CI 1.2-1.7; HR 2.0 95% CI 1.6-2.5) during long-term follow-up, respectively. Patients with 2- and 3-AVB received extended medical treatment compared with 1-AVB at the time of discharge. CONCLUSION Polyvascular atherosclerotic disease in PAD patients is independently associated with an increased risk for all-cause and cardiovascular mortality during long-term follow-up.

Association between chronic obstructive pulmonary disease and chronic kidney disease in vascular surgery patients

BACKGROUND Chronic obstructive pulmonary disease (COPD) is recognized as a source of systemic inflammation and is associated with the development of cardiovascular disease. However, little is known about the association between COPD and chronic kidney disease (CKD). Therefore, we investigated the relationship between COPD and CKD and the association between COPD and mortality in patients with CKD. METHODS We conducted a cohort study of 3358 vascular surgery patients between 1990 and 2006. CKD was defined according to the Modification of Diet in Renal Disease equation as an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2). In addition, the patients were divided into three categories based on the baseline estimated GFR: > or =90 mL/min/1.73 m(2); 60-89 mL/min/1.73 m(2) and <60 mL/min/1.73 m(2). Multivariable logistic regression analysis was used to evaluate the independent association between prevalent COPD and CKD. RESULTS The prevalence of COPD was inversely related to kidney function. COPD was present in 47, 38 and 32% of patients with an estimated GFR <60, 60-89 and > or =90 mL/min/1.73 m(2), respectively. COPD was independently associated with CKD (OR 1.22; 95% CI 1.03-1.44; P = 0.03). This association was strongest in patients with moderate COPD (OR 1.33; 95% CI 1.07-1.65; P = 0.01). Both moderate and severe COPD were associated with increased long-term mortality in patients with CKD (HR 1.27; 95% CI 1.03-1.56; P = 0.03 and HR 1.61; 95% CI 1.10-2.35; P = 0.01, respectively), compared to patients without COPD. CONCLUSIONS Our findings indicate that COPD is moderately associated with CKD in a large cohort of vascular surgery patients. In addition, moderate and severe COPD are related to increased long-term mortality in patients with CKD.