Pavel J. Levy

Analysis of risk factors for myocardial infarction and cardiac mortality after major vascular surgery

Background Patients undergoing vascular surgical procedures are at high risk for perioperative myocardial infarction (PMI). This study was undertaken to identify predictors of PMI and in-hospital death in major vascular surgical patients. Methods From the Vascular Surgery Registry (6,948 operations from January 1989 through June 1997) the authors identified 107 patients in whom PMI developed during the same hospital stay. Case–control patients (patients without PMI) were matched at a 1×:×1 ratio with index cases according to the type of surgery, gender, patient age, and year of surgery. The authors analyzed data regarding preoperative cardiac disease and surgical and anesthetic factors to study association with PMI and cardiac death. Results By using univariable analysis the authors identified the following predictors of PMI: valvular disease (P = 0.007), previous congestive heart failure (P = 0.04), emergency surgery (P = 0.02), general anesthesia (P = 0.03), preoperative history of coronary artery disease (P = 0.001), preoperative treatment with &bgr;-blockers (P = 0.003), lower preoperative (P = 0.03) and postoperative (P = 0.002) hemoglobin concentrations, increased bleeding rate (as assessed from increased cell salvage;P = 0.025), and lower ejection fraction (P = 0.02). Of the 107 patients with PMI, 20.6% died of cardiac cause during the same hospital stay. The following factors increased the odds ratios for cardiac death: age (P = 0.001), recent congestive heart failure (P = 0.01), type of surgery (P = 0.04), emergency surgery (P = 0.02), lower intraoperative diastolic blood pressure (P = 0.001), new intraoperative ST-T changes (P = 0.01), and increased intraoperative use of blood (P = 0.005). Patients who underwent coronary artery bypass grafting, even more than 12 months before index surgery, had a 79% reduction in risk of death if they had PMI (P = 0.01). Multivariable analysis revealed preoperative definitive diagnosis of coronary artery disease (P = 0.001) and significant valvular disease (P = 0.03) were associated with increased risk of PMI. Congestive heart failure less than 1 yr before index vascular surgery (P = 0.0002) and increased intraoperative use of blood (P = 0.007) were associated with cardiac death. The history of coronary artery bypass grafting reduced the risk of cardiac death (P = 0.04) in patients with PMI. Conclusions The in-hospital cardiac mortality rate is high for patients who undergo vascular surgery and experience clinically significant PMI. Stress of surgery (increased intraoperative bleeding and aortic, peripheral vascular, and emergency surgery), poor preoperative cardiac functional status (congestive heart failure, lower ejection fraction, diagnosis of coronary artery disease), and preoperative history of coronary artery bypass grafting are the factors that determine perioperative cardiac morbidity and mortality rates.

Value of Noninvasive Hemodynamics to Achieve Blood Pressure Control in Hypertensive Subjects

Abnormal hemodynamics play a central role in the development and perpetuation of high blood pressure. We hypothesized that hypertension therapy guided by noninvasive hemodynamics with impedance cardiography could aid primary care physicians in reducing blood pressure more effectively. Uncontrolled hypertensive patients on 1 to 3 medications were randomized by 3:2 ratio to either a standard arm or hemodynamic arm that used impedance cardiography (BioZ, CardioDynamics). Each patient completed 5 study visits with a 2-week washout period followed by 3 months of treatment. A total of 164 patients from 11 centers completed the study, 95 in the standard arm and 69 in the hemodynamic arm. At baseline and after washout, there were no differences between arms in number of medications or demographic, blood pressure, or hemodynamic characteristics. Systolic blood pressure reductions in the hemodynamic arm were greater from baseline (19 mm Hg versus 11 mm Hg; P<0.01) and after washout (25 mm Hg versus 19 mm Hg; P<0.05). Diastolic blood pressure reductions were also greater in the hemodynamic arm from baseline (12 mm Hg versus 5 mm Hg; P<0.001) and after washout (17 mm Hg versus 10 mm Hg; P<0.001). The hemodynamic arm achieved goal blood pressure (<140/90 mm Hg) more frequently (77% versus 57%; P<0.01) and a more aggressive blood pressure level (<130/85 mm Hg) more frequently (55% versus 27%; P<0.0001). These study results indicate that antihypertensive therapy guided by impedance cardiography in uncontrolled hypertensive patients on ≥1 medications is more effective than standard care.

Lower extremity ischemia in adults younger than forty years of age: A community-wide survey of premature atherosclerotic arterial disease

A retrospective community-wide survey identified 109 patients younger than 40 years of age with lower extremity ischemia: 72 men and 37 women, mean age 36 years (range 25 to 40 years), black-to-white ratio-1:1. Initially, 66 patients had claudication and 43 had severe ischemia. Cardiovascular risk factors were smoking (85%), hypertension (47%), coronary artery disease (30%), hyperlipidemia (27%), diabetes (25%), and visceral arteriopathy (17%). Unique risk factors included hypercoagulability (15%) and clinical arterial hypoplasia (15%). Twenty-three (21%) patients were treated medically; 74 (68%) underwent primary revascularization and 12 (11%) primary major limb amputation. Forty-six (53%) patients required secondary procedures, of which 34 (74%) were performed within 1 year of primary intervention. A total of 29 (27%) patients ultimately required amputation (10 bilateral). Women had higher prevalence of diabetes (p < 0.01), arterial hypoplasia (p < 0.05), and tendency for more severe ischemia (p = 0.11). No racial differences in severity of symptoms or outcome of treatment were found. By multiple logistic regression analysis, typical cardiovascular risk factors did not predict severity of symptoms, need for surgical treatment, or outcome. However, diabetes was associated with tissue loss (p < 0.05) and primary amputation (p < 0.001). Further, adjusted odds ratios indicate that arterial hypoplasia had a protective effect on distal vasculature (p < 0.05) and predicting need for revascularization (p < 0.05), but not on treatment failure. Hypercoagulability had the highest predictive value for presence of severe ischemia (p < 0.05), need for primary amputation (p < 0.01), and early failure of surgical treatment (p < 0.05).

Inhibition of platelet aggregability by losartan in essential hypertension

Most clinical events associated with hypertension have a thrombotic component. Losartan is a selective, competitive antagonist of the thromboxane A2 receptor in experiments performed in isolated vascular strips and in human and rat platelet-enriched plasma. In this study, we investigated for the first time whether losartan at therapeutic doses has an effect on platelet aggregability and indexes of fibrinolysis in essential hypertensive subjects. Changes in the dose-response curve to platelet aggregation induced by the thrombin receptor-activating peptide SFLRRN-NH2 were determined in 9 patients (56% men, 72% white; mean age 52.8 years) with stage I or II essential hypertension and in 9 untreated healthy volunteers. After a 4-week washout period, hypertensive subjects received 2 weeks of placebo followed by 4 weeks of losartan 50 mg/day. Both subjects and end points were blinded for treatment assignment. In addition, plasminogen activator inhibitor type 1 antigen and von Willebrand antigen were studied in all patients and controls. Four weeks of losartan produced a statistically significant (p <0.05) increase in the concentration of SFLRRN-NH2 required to induce a half-maximal response in platelet aggregation extent and rate 4 weeks after initiation of treatment. The decrease in platelet aggregability was independent of blood pressure control and the effects of gender and age. Losartan had no effect on plasma concentrations of plasminogen activator inhibitor-1 and von Willebrand factor in hypertensive subjects. These data demonstrate for the first time a novel antiplatelet effect of losartan at therapeutic doses, which was independent of changes in blood pressure, plasma markers of fibrinolytic activity, and endothelial perturbation.

The Hypertension-Lipid Connection: Insights into the Relation between Angiotensin II and Cholesterol in Atherogenesis

Clinical data and experimental studies have established the important role of abnormal lipid metabolism in the causation of atherosclerosis and enthroned the hydroxymethylglutaryl coenzyme reductase inhibitors (statins) as a mainstay in management of patients with coronary heart disease. However, emerging experimental data underline the role of vascular renin-angiotensin systems in mediating the early stages of vascular endothelial dysfunction and inflammation as prerequisites for unleashing the cascade of cellular and molecular events that lead to the deposition of foam cells and their eventual progression to the atherosclerotic plaque. We discuss here the biological effects of statins and angiotensin II in the evolution of atherogenesis, underscoring possible links between statins and angiotensin receptor blockers. From the assessment of the commonality of effects resulting from the nonlipidic actions of statins and angiotensin II on the process of atherogenesis, we develop the argument that dyslipidemia may influence the ability to control blood pressure in hypertensive subjects and hypothesize that the combined use of statins and blockers of the renin-angiotensin system may have an additive effect in the management of hypertensive subjects.

Renin-angiotensin system as a therapeutic target in managing atherosclerosis.

Clinical and experimental evidence suggests that the pathways by which hypertension and dyslipidemia lead to vascular disease may overlap and that angiotensin II (Ang II) is involved in restructuring of the arterial wall in both atherosclerosis and hypertension. Ang II represents a potent proinflammatory agent promoting recruitment of monocytes into the vascular intima. Ang II also indirectly facilitates transformation of macrophages and smooth muscle cells into foam cells by promoting superoxide radical formation (via NADP/NADPH oxidase stimulation). The oxidative stress produced by Ang II leads to enhanced low-density lipoprotein oxidation and degradation of nitric oxide, an important vascular protective molecule capable of retarding atherosclerosis progression. The importance of the renin–angiotensin system (RAS) in atherogenesis is highlighted by studies in animal models as well as human beings indicating that inhibition of angiotensin-converting enzyme or blockade of type 1 Ang II receptors retards the development of atherosclerotic lesions. In light of a causal and central role of Ang II in atherogenesis, blockade of the RAS represents an important therapeutic consideration in the prevention and treatment of atherosclerotic disease.

Associations between renovascular disease and prevalent cardiovascular disease in the elderly: A population-based Study

Atherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity =1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African-Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 ±4.9 years underwent RDS examination. RVD was present in 57 participants (6.8%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p=0.002), previous myocardial infarction (p< 0.001), = 25% diameter-reducing internal carotid artery stenosis (p= 0.010), increased carotid intimal medial thickness (p= 0.003), and major electrocardiographic abnormalities (p= 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.

Epidemiology and pathophysiology of peripheral arterial disease.

Evidence that both asymptomatic and symptomatic peripheral arterial disease (PAD) represent an independent risk for cardiovascular morbidity and mortality has triggered a resurgence in epidemiologic and clinical interest in PAD. Between 8 and 12 million people in the United States are presumed to have PAD, and as the US population ages the incidence of PAD is expected to increase. Epidemiologic studies have shown that the prevalence of PAD among men and women is similar, and autopsy studies of young adults have shown a high frequency of advanced atherosclerotic lesions in distal abdominal aorta by the second decade of life. The pathophysiology of PAD is complex and has not been studied thoroughly. Additional research to understand the pathophysiologic mechanisms in disease-specific circulatory beds is crucial for the advancement of medical therapy for PAD.

Premature Lower Extremity Atherosclerosis: Clinical Aspects

&NA; Peripheral arterial disease (PAD) involving the lower extremities is presumably a disease of the elderly. The awareness of PAD in the general population, and in younger adults in particular, is low. Atherosclerosis is the major cause of lower limb ischemia in the young. Young adults with clinical manifestations of premature lower extremity atherosclerosis (PLEA) typically have multiple cardiovascular risk factors and the majority are smokers, with strong family history of cardiovascular disease, and typically have chronic symptoms of claudication at diagnosis. Frequently these symptoms are either not reported in a timely manner by the patients or are attributed to other, presumably more common causes of leg pain in the young. More than 70% of patients with PLEA have angiographic evidence of severe aortoiliac disease. The results of surgical revascularizations in young adults are inferior to those reported in older patients. Younger adults typically require multiple revascularizations with relatively high amputation rate. We conclude that PAD should be considered in adults with multiple risk factors regardless of their age if appropriate symptoms are present. There is a need for increased public health awareness for premature lower extremity atherosclerosis.

Carotid endarterectomy in adults 50 years of age and younger: A retrospective comparative study

PURPOSE Atherosclerotic carotid artery stenosis (CAS) is the most common cause of stroke in young adults. We retrospectively studied clinical characteristics of premature CAS and the safety and durability of carotid endarterectomy (CEA) in 56 patients 50 years of age or younger (mean, 46.4 years; 34 (60%) males; group I) who underwent primary CEA at the Cleveland Clinic between 1983 and 1993. METHODS The patients were identified from the Vascular Surgery Registry and were compared with 202 randomly selected patients 60 years of age and older (mean, 69.3 years; group II) who were frequency-matched by gender and the year of primary CEA. Carotid shunting was used routinely, and the arteriotomy was patched in the majority of cases. Patients were followed-up for mean of 47.2 months (group I) and 46.0 months (group II). RESULTS No significant differences were found in the indications for CEA (symptomatic CAS, 49% in group I vs 48% in group II) or the prevalence of diabetes, coronary diseases, and lower extremity arterial disease. Younger adults were more likely to have a history of smoking (93% vs 76%; p = 0.005), hypertension (71% vs 52%; p = 0.006), premature menopause (57% vs 18%; p < 0.001) and had lower levels of high-density lipoprotein cholesterol (p = 0.03). There were no in-hospital deaths. Perioperative strokes in the distribution of the operated artery occurred within 24 hours in one younger patient (1.8%) and in one older patient (0.5%). This was attributed to early carotid thrombosis in the young patient. Major late postoperative neurologic complications were documented in one young patient (1.8%) and six older patients (3%). Patients in group I were at significantly higher risk for recurrent carotid stenosis (risk ratio, 3.1; 95% confidence interval [CI], 1.3 to 7.3; p = 0.010); younger individuals remained at significantly higher risk for recurrent stenosis even after adjusting for smoking and hypertension (risk ratio, 3.7; 95% CI, 1.5 to 9.4; p = 0.006). By life-table analysis, younger adults tended to have a higher rate of late reoperations (p = 0.065). CONCLUSIONS CEA can be safely performed in young adults with premature CAS, although younger individuals appear to have higher rates of recurrent carotid stenosis compared with older counterparts.