Vascular surgery patients are at increased risk of adverse cardiovascular events because of silent coronary artery disease and an increased propensity for left ventricular dysfunction. The Revised Cardiac Risk Index is commonly used for preoperative risk stratification. Aortic valve calcium is associated with cardiovascular mortality in the general population. The present study evaluated the prognostic implications of aortic valve calcium on 30-day postoperative and long-term outcomes in vascular surgery patients. Echocardiographic aortic valve evaluation was completed in 1,172 vascular surgery patients. Aortic valve sclerosis was defined by the presence of thickening and/or calcium of ≥1 cusps of a tricuspid aortic valve not inducing stenosis (i.e., with a maximal velocity at continuous Doppler of <2.5 m/s). Stenosis was defined as a maximum velocity of >2.5 m/s. Troponin-T measurements and electrocardiograms were performed routinely after surgery. The study end points were the composite of postoperative cardiovascular events and long-term mortality. Aortic valve sclerosis was present in 416 patients (36%), and aortic valve stenosis was present in 30 patients (3%). After multivariate regression analyses adjusted for age, gender, Revised Cardiac Risk Index, hypertension, hypercholesterolemia, and medication use, aortic valve sclerosis was not associated with either the postoperative or long-term outcomes. In contrast, aortic valve stenosis was associated with a greater postoperative and long-term event rate (odds ratio 3.9, 95% confidence interval 1.7 to 8.7; and hazard ratio 2.1, 95% confidence interval 1.2 to 3.7, respectively). In conclusion, the present study has shown that aortic valve calcium is common in vascular surgery patients. Its presence is associated with negative postoperative and long-term outcomes.
Patients with peripheral arterial disease undergoing vascular surgery are known to be at increased risk of perioperative and late cardiovascular (CV) events because of silent coronary artery disease and a greater propensity for left ventricular dysfunction. The Revised Cardiac Risk Index (RCRI) is commonly used for preoperative risk stratification in this patient population. Aortic valve calcium is associated with CV mortality in the general population. It is unknown whether the presence of aortic valve calcium increases the risk of CV events in patients with peripheral arterial disease.
The aim of the present study was to evaluate the prognostic implications of aortic valve calcium on the 30-day postoperative and long-term outcomes in patients with peripheral arterial disease requiring vascular surgery.
Methods
The present prospective cohort study included 1,484 vascular surgery patients treated at the Erasmus Medical Center (Rotterdam, The Netherlands) from 2002 to 2011. The institutional review board approved the study, and the study complied with the Declaration of Helsinki. The patients were screened before surgery at the outpatient clinic using physical examination, laboratory measurements, electrocardiograms, and lung function tests.
Before surgery, a detailed medical history was obtained from every patient. The baseline characteristics included the following: age, gender, blood pressure, coronary heart disease (angina pectoris, previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting), cerebrovascular disease (history of stroke or transient ischemic attack), renal dysfunction (estimated glomerular filtration rate <60 ml/min/1.73 m 2 ), heart failure (by history), diabetes mellitus (history or antidiabetic medication requirement), hypertension (blood pressure ≥140/90 mm Hg in nondiabetics and ≥130/80 mm Hg in diabetics or antihypertensive medication requirement), hypercholesterolemia (low-density lipoprotein cholesterol ≥135 mg/dl or lipid-lowering medication requirement), chronic obstructive pulmonary disease (according to the Global Initiative on Obstructive Lung Diseases classification), and smoking status. Medication use was recorded for aspirin, oral anticoagulants, β blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, diuretics, nitrates, and statins.
The cardiac risk score was determined for every patient using the RCRI. The RCRI assigns 1 point to each of the following characteristics: high-risk surgery, coronary heart disease, history of congestive heart failure, history of cerebrovascular disease, insulin therapy for diabetes mellitus, and renal insufficiency (serum creatinine >2.0 mg/dl).
Aortic valve evaluation with transthoracic echocardiography was performed preoperatively or within 30 days postoperatively, using a portable Acuson Cypress ultrasound system (Acuson, A Siemens, Mountain View, California) with a 7V3c transducer or a portable Vivid-I ultrasound System (Vivid-I, GE Healthcare, Solingen, Germany) with a 3S-RS transducer. The aortic valve evaluation included assessment of the cusp anatomy and valvular calcium. Continuous wave Doppler echocardiography was used to measure aortic jet velocity. Aortic valve sclerosis (AVS) was defined by the presence of thickening and/or calcium of ≥1 cusps of a tricuspid valve not inducing stenosis (i.e., with a maximal velocity <2.5 m/s). Aortic valve stenosis (AoS) was defined as a jet velocity >2.5 m/s. That jet velocity was chosen, because this is the strongest predictor of clinical outcomes in patients with AoS. Patients with moderate AoS (jet velocity 3.0 to 4.0 m/s) or severe AoS (jet velocity >4.0 m/s) were referred to a cardiologist for regular follow-up. Patients with unstable cardiac conditions or severe aortic stenosis requiring preoperative intervention were excluded.
Serial electrocardiograms and troponin-T measurements were routinely obtained before surgery and postoperatively on days 1, 3, and 7. The study end points were 30-day CV events and long-term mortality. The 30-day CV events were a composite of nonfatal myocardial infarction, new or worsened congestive heart failure, severe cardiac arrhythmias (defined as the presence of a sustained cardiac rhythm disturbance that required urgent medical intervention), stroke (including transient ischemic attack), CV mortality (any death from a cerebrovascular cause, including death after myocardial infarction, congestive heart failure, arrhythmia, stroke, and surgery-related bleeding complications or sudden unexpected death), and asymptomatic troponin-T release. Myocardial infarction was defined as the characteristic increase and decrease of (postoperative) troponin-T levels greater than the 99th percentile with either electrocardiographic or clinical signs of myocardial ischemia. The troponin-T level was measured using a whole blood rapid test (TropT, version 2, Roche Diagnostics, Mannheim, Germany). The 30-day follow-up data was completed from patients’ visits to the outpatient clinic. For patients still admitted or readmitted at the Erasmus Medical Center, the follow-up data was completed using the Erasmus Medical Center medical records. Long-term mortality was ascertained from the municipal civil registries. The follow-up data were complete for all patients.
Continuous variables are described as the mean ± SD and dichotomous data as numbers and percentages. Continuous data were compared using analysis of variance and categorical data using chi-square tests. Cumulative long-term survival was determined using the Kaplan-Meier method and compared using the log-rank test. The prognostic value of AVS and AoS toward the 30-day and long-term end points was evaluated with logistic and Cox regression analyses, respectively. Multivariate analyses were primarily adjusted for predefined potential confounders (age, gender, RCRI, hypertension, and hypercholesterolemia). A second multivariate analysis was performed to adjust for medication with known beneficial effects (aspirin, β blockers, statins, and ACE inhibitors). For all tests, a p value <0.05 (2-sided) was considered significant. All statistical analyses were performed using SPSS, version 17.0, statistical software (SPSS, Chicago, Illinois).
Results
The study population consisted of 1,484 vascular surgery patients, of whom 1,172 had complete echocardiographic aortic valve data available. Open vascular surgery was performed in 660 patients (56%), and 511 (44%) underwent endovascular surgery. Of the 1,172 patients, 338 (29%) underwent lower extremity artery repair, 569 (49%) underwent abdominal aortic repair, and 251 (21%) underwent carotid artery repair. General anesthesia was applied in 97% of the open vascular surgery cases and 45% of the endovascular surgery cases. Spinal and local (infiltration) anesthesia was used in 11% and 44% of patients undergoing endovascular surgery, respectively.
The mean age of the study population was 68 ± 10 years, and most (74%) were men. AVS was diagnosed in 416 patients (36%) and AoS in 30 patients (3%). Of these patients, 14 (1.2%) had mild aortic stenosis (peak velocity 2.5 to <3.0 m/s), 9 (0.8%) had moderate aortic stenosis (peak velocity 3.0 to <4.0 m/s), and 7 (0.6%) had severe aortic stenosis (peak velocity >4.0 m/s).
The baseline characteristics of the study population according to aortic valve calcium are listed in Table 1 . The patients with aortic valve calcium were older (p <0.001) and had a greater incidence of coronary heart disease (p = 0.005), renal dysfunction (p <0.001), diabetes mellitus (p = 0.036), and hypertension (p <0.001). Patients with aortic valve calcium had a greater RCRI compared to patients with normal aortic valves (p <0.001). Regarding medication, no differences were found in the use of aspirin, calcium antagonists, ACE inhibitors, angiotensin II antagonists, diuretics, nitrates, and statins. However, patients with aortic valve calcium more often received oral anticoagulants (p = 0.012) and β blockers (p = 0.015).
| Characteristic | Normal AoV (n = 726) | AVS (n = 416) | AoS (n = 30) | p Value |
|---|---|---|---|---|
| Age (years) | 67 ± 11 | 71 ± 9 | 75 ± 7 | <0.001 |
| Men | 536 (74%) | 313 (75%) | 21 (70%) | 0.754 |
| Coronary heart disease | 270 (37%) | 185 (45%) | 18 (60%) | 0.005 |
| Cerebrovascular disease | 234 (32%) | 149 (36%) | 10 (33%) | 0.466 |
| Renal dysfunction | 147 (20%) | 139 (33%) | 12 (40%) | <0.001 |
| Heart failure | 58 (8%) | 50 (12%) | 2 (7%) | 0.070 |
| Diabetes mellitus | 156 (22%) | 117 (28%) | 6 (20%) | 0.036 |
| Hypertension | 449 (62%) | 321 (77%) | 21 (70%) | <0.001 |
| Hypercholesterolemia | 660 (91%) | 374 (90%) | 24 (80%) | 0.135 |
| Chronic obstructive pulmonary disease | 220 (45%) | 153 (45%) | 9 (43%) | 0.980 |
| Smoker, current | 323 (45%) | 165 (40%) | 15 (50%) | 0.210 |
| Surgery type | ||||
| Open | 400 (55%) | 242 (58%) | 18 (60%) | 0.734 |
| Endovascular | 326 (45%) | 173 (42%) | 12 (40%) | 0.251 |
| Medication | ||||
| Aspirin | 488 (68%) | 270 (65%) | 17 (57%) | 0.342 |
| Oral anticoagulants | 105 (15%) | 89 (21%) | 6 (20%) | 0.012 |
| β Blockers | 575 (80%) | 360 (87%) | 25 (83%) | 0.015 |
| Calcium antagonists | 125 (17%) | 93 (22%) | 6 (20%) | 0.114 |
| Angiotensin-converting enzyme inhibitors | 196 (27%) | 132 (32%) | 10 (33%) | 0.230 |
| Angiotensin II antagonists | 117 (16%) | 89 (21%) | 6 (20%) | 0.090 |
| Diuretics | 163 (23%) | 119 (29%) | 8 (27%) | 0.074 |
| Nitrates | 62 (9%) | 52 (13%) | 3 (10%) | 0.106 |
| Statins | 574 (80%) | 336 (81%) | 19 (63%) | 0.073 |
| Revised cardiac risk score | <0.001 | |||
| 0–1 Risk factor | 462 (64%) | 198 (48%) | 12 (40%) | |
| 2 Risk factors | 176 (24%) | 131 (32%) | 9 (30%) | |
| ≥3 Risk factors | 86 (12%) | 86 (21%) | 9 (30%) |
During the 30-day follow-up period, 203 patients (17%) experienced a CV event. Of these 203 patients, 115 patients (16%) had a normal aortic valve compared to 72 (17%) with AVS and 16 (53%) with AoS (p <0.001; Table 2 ). After adjustment for potential confounders, AoS, but not AVS, was associated with an increased risk of CV events at 30 days (AoS, odds ratio [OR] 3.9, 95% confidence interval [CI] 1.7 to 8.7; and AVS, OR 0.8, 95% CI 0.6 to 1.1; Table 2 ). These results were not influenced by a correction for medication use in a second multivariate analysis. RCRI ≥2 points and age were other risk factors associated with postoperative CV events (RCRI 2 points, OR 3.2, 95% CI 2.2 to 4.7; RCRI ≥3 points, OR 5.0, 95% CI 3.2 to 7.6; and age, OR 1.0, 95% CI 1.0 to 1.1).
| Variable | Patients (%) | Univariate Analysis | Multivariate Analysis 1 ⁎ | Multivariate Analysis 2 † |
|---|---|---|---|---|
| 30-Day cardiovascular events ‡ | ||||
| Normal aortic valve | 115/726 (16%) | Reference | Reference | Reference |
| Aortic valve sclerosis | 72/416 (17%) | 1.1 (0.8–1.6) | 0.8 (0.6–1.1) | 0.8 (0.5–1.1) |
| Aortic valve stenosis | 16/30 (30%) | 6.1 (2.9–12.9) | 3.9 (1.7–8.7) | 3.8 (1.7–8.6) |
| Long-term mortality § | ||||
| Normal aortic valve | 140/726 (19%) | Reference | Reference | Reference |
| Aortic valve sclerosis | 98/416 (24%) | 1.4 (1.1–1.8) | 1.0 (0.7–1.3) | 0.9 (0.7–1.2) |
| Aortic valve stenosis | 15/30 (50%) | 3.6 (2.1–6.2) | 2.1 (1.2–3.7) | 2.0 (1.2–3.4) |
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