Metabolic syndrome, diabetes and cardiovascular events: current controversies and recommendations.

Metabolic syndrome is now present in up to 40% of the United States adult population and is associated with a nearly a two fold increase in cardiovascular events, independent of the presence of diabetes mellitus. The concept of the metabolic syndrome as clinical syndrome has recently been challenged, however, and controversy exists as to whether the metabolic syndrome adds to cardiovascular risk above and beyond the sum of its independent metabolic components. Given the epidemic of obesity in both industrialized and third world countries, this issue is of great importance. The current article puts this controversy into perspective and explores the association of metabolic syndrome with both accelerated cardiovascular risk and the risk of development of type 2 diabetes. The pathophysiology of the increased risk of cardiovascular disease in diabetes associated with metabolic syndrome is discussed and the importance of early recognition of metabolic syndrome and potential role of addressing insulin resistance is stressed. Clearly more data is needed, but it is safe to say that metabolic syndrome is a worldwide epidemic in association with central obesity and underlying insulin resistance, which will propel a marked increase in cardiovascular events and diabetes mellitus in the years to come. Further research is needed to understand the role of more aggressive therapy in preventing type 2 diabetes and cardiovascular events in the population.

Diastolic abnormalities in young asymptomatic diabetic patients assessed by pulsed Doppler echocardiography.

Indexes of left ventricular diastolic filling were measured by pulsed Doppler echocardiography in 21 insulin-dependent diabetic patients and 21 control subjects without clinical evidence of heart disease. No patient had chest pain or electrocardiographic changes during exercise testing. The mean age of patients was 32 years. All patients had a normal ejection fraction. Six (29%) of the 21 diabetic patients had evidence of diastolic dysfunction as assessed by the presence of at least two abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in diabetic compared with control subjects (1.24 +/- 0.21 versus 1.66 +/- 0.30, p. less than 0.001). Atrial filling velocity was significantly increased in diabetic patients (74.3 +/- 16.7 versus 60.3 +/- 12.2 cm/s, p less than 0.004), whereas early filling velocity was reduced by a nearly significant degree (88.8 +/- 12.6 versus 98.5 +/- 18.8 cm/s, p less than 0.057). The atrial contribution to stroke volume as assessed by area under the late diastolic filling envelope compared to total diastolic area was also significantly increased in diabetic compared with control subjects (35 versus 27%, p less than 0.001). Left ventricular diastolic filling abnormalities in diabetic patients did not correlate with duration of diabetes, retinopathy, nephropathy or peripheral neuropathy. These data suggest that approximately one-third of such patients have subclinical myocardial dysfunction unrelated to accelerated atherosclerosis. Doppler echocardiography may offer a reliable noninvasive means to assess diastolic function and to follow up diabetic patients serially for any deterioration in cardiac status before the appearance of clinical symptoms.

Sequential combination thrombolytic therapy for acute myocardial infarction: results of the Pro-Urokinase and t-PA Enhancement of Thrombolysis (PATENT) Trial.

OBJECTIVES: The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction. BACKGROUND: Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo. METHODS: In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and given a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min. RESULTS: Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death. CONCLUSIONS: A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.

Determination of aortic valve area in valvular aortic stenosis by direct measurement using intracardiac echocardiography: a comparison with the Gorlin and continuity equations.

OBJECTIVES: This study sought to 1) show that intracardiac echocardiography can allow direct measurement of the aortic valve area, and 2) compare the directly measured aortic valve area from intracardiac echocardiography with the calculated aortic valve area from the Gorlin and continuity equations. BACKGROUND: Intracardiac echocardiography has been used in the descriptive evaluation of the aortic valve; however, direct measurement of the aortic valve area using this technique in a clinical setting has not been documented. Despite their theoretical and practical limitations, the Gorlin and continuity equations remain the current standard methods for determining the aortic valve orifice area. METHODS: Seventeen patients underwent intracardiac echocardiography for direct measurement of the aortic valve area, including four patients studied both before and after valvuloplasty, for a total of 21 studies. Immediately after intracardiac echocardiography, hemodynamic data were obtained from transthoracic echocardiography and cardiac catheterization. RESULTS: Adequate intracardiac echocardiographic images were obtained in 17 (81%) of 21 studies. The average aortic valve area (mean +/- SD) determined by intracardiac echocardiography for the 13 studies in the Gorlin analysis group was 0.59 +/- 0.18 cm2 (range 0.37 to 1.01), and the average aortic valve area determined by the Gorlin equation was 0.62 +/- 0.18 cm2 (range 0.31 to 0.88). The average aortic valve area determined by intracardiac echocardiography for the 17 studies in the continuity analysis group was 0.66 +/- 0.23 cm2 (range 0.37 to 1.01), and that for the continuity equation was 0.62 +/- 0.22 cm2 (range 0.34 to 1.06). There was a significant correlation between the aortic valve area determined by intracardiac echocardiography and the aortic valve area calculated by the Gorlin (r = 0.78, p = 0.002) and continuity equations (r = 0.82, p < 0.0001). CONCLUSIONS: In the clinical setting, intracardiac echocardiography can directly measure the aortic valve area with an accuracy similar to the invasive and noninvasive methods currently used. This study demonstrates a new, quantitative use for intracardiac echocardiographic imaging with many potential clinical applications.

Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1,081 vascular surgical candidates.

OBJECTIVES: This study sought to develop and validate a Bayesian risk prediction model for vascular surgery candidates. BACKGROUND: Patients who require surgical treatment of peripheral vascular disease are at increased risk of perioperative cardiac morbidity and mortality. Existing prediction models tend to underestimate risk in vascular surgery candidates. METHODS: The cohort comprised 1,081 consecutive vascular surgery candidates at five medical centers. Of these, 567 patients from two centers ("training" set) were used to develop the model, and 514 patients from three centers were used to validate it ("validation" set). Risk scores were developed using logistic regression for clinical variables: advanced age (>70 years), angina, history of myocardial infarction, diabetes mellitus, history of congestive heart failure and prior coronary revascularization. A second model was developed from dipyridamole-thallium predictors of myocardial infarction (i.e., fixed and reversible myocardial defects and ST changes). Model performance was assessed by comparing observed event rates with risk estimates and by performing receiver-operating characteristic curve (ROC) analysis. RESULTS: The postoperative cardiac event rate was 8% for both sets. Prognostic accuracy (i.e., ROC area) was 74 +/- 3% (mean +/- SD) for the clinical and 81 +/- 3% for the clinical and dipyridamole-thallium models. Among the validation sets, areas were 74 +/- 9%, 72 +/- 7% and 76 +/- 5% for each center. Observed and estimated rates were comparable for both sets. By the clinical model, the observed rates were 3%, 8% and 18% for patients classified as low, moderate and high risk by clinical factors (p<0.0001). The addition of dipyridamole-thallium data reclassified >80% of the moderate risk patients into low (3%) and high (19%) risk categories (p<0.0001) but provided no stratification for patients classified as low or high risk according to the clinical model. CONCLUSIONS: Simple clinical markers, weighted according to prognostic impact, will reliably stratify risk in vascular surgery candidates referred for dipyridamole-thallium testing, thus obviating the need for the more expensive testing. Our prediction model retains its prognostic accuracy when applied to the validation sets and can reliably estimate risk in this group.

Routine perioperative dipyridamole 201Tl imaging in diabetic patients undergoing vascular surgery.

OBJECTIVE: To assess the utility of dipyridamole thallium testing in symptomatic and asymptomatic patients with diabetes undergoing vascular surgery. RESEARCH DESIGN AND METHODS: Dipyridamole 201Tl myocardial scintigraphy was performed preoperatively in 93 consecutive patients with diabetes undergoing peripheral vascular procedures. The utility of clinical and thallium variables in predicting cardiovascular complications was assessed. RESULTS: Two groups of patients were identified: group A (36 patients) without clinical evidence of cardiac disease and group B (57 patients) with clinical evidence of cardiac disease. Dipyridamole thallium scans were abnormal in 21 of 36 (58%) of group A patients compared with 53 of 57 (93%) of group B patients (P < 0.0001). Compared with group B patients with perfusion defects, group A patients with perfusion abnormalities tended to have fewer defects per scan (2.7 +/- 1.5 vs. 3.6 +/- 1.9, P = 0.05). No perioperative cardiac complications occurred in group A patients while perioperative cardiac complications occurred in 9 of 57 (16%, 95% CI 7-28%) group B patients (P = 0.01). For the entire study population, the complication rate was 10%. CONCLUSIONS: Diabetic individuals without clinical markers for coronary artery disease appear to be at low risk for adverse postoperative cardiac events after vascular surgery. Preoperative myocardial perfusion imaging may add little to cardiovascular risk assessment in this subgroup of patients with diabetes.

Long-term prognostic value of preoperative dipyridamole thallium imaging and clinical indexes in patients with diabetes mellitus undergoing peripheral vascular surgery.

The objective of this study is to assess the prognostic impact of preoperative dipyridamole thallium imaging and clinical variables on the long-term outcome of diabetic patients undergoing peripheral vascular surgery. Complete follow-up was obtained in 101 consecutive patients with diabetes mellitus undergoing routine dipyridamole thallium scintigraphy before vascular surgery (mean 4.2 +/- 3.2 years, range 1 month to 11 years). Low risk was defined by diabetes alone with a normal resting electrocardiogram. High risk was defined as a history of angina, myocardial infarction, congestive heart failure, or resting electrocardiogram abnormalities. There were 71 deaths in 98 patients discharged alive from the hospital (median survival 4.4 years). Age, the presence of resting electrocardiogram abnormalities, and an abnormal thallium scan were independent predictors of late death. After adjusting for age >70 years and thallium abnormalities, high-risk patients had a death rate 4.8 times (95% confidence interval 1.7 to 13.4, p <0.002) greater than low-risk patients. The presence of >2 reversible thallium defects was useful in further risk stratification of both low- and high-risk patients. Low-risk patients with >2 reversible defects had a median survival of 4.0 years compared with 9.4 years in those with < or =2 reversible defects (p <0.001). Similarly, high-risk patients with < or =2 reversible defects had an intermediate median survival rate of 4.7 years compared with 1.8 years in the group with >2 reversible defects (p <0.001). Therefore, advanced age and the presence of resting electrocardiographic or thallium abnormalities identifies a subset of diabetic patients with a poor long-term outcome after vascular surgery. Combined clinical and thallium variables may identify a population in whom intensive medical or surgical interventions may be warranted to reduce both perioperative and late cardiac events.

Left ventricular filling abnormalities in asymptomatic morbid obesity.

Indexes of left ventricular (LV) diastolic filling were measured by pulse Doppler echocardiography in 16 asymptomatic morbidity obese patients presenting for bariatric surgery and were compared with an age- and sex-matched lean control population. No patient had concomitant disorders known to affect diastolic function. All patients had normal systolic function. LV wall thickness and internal dimension were measured in order to calculate LV mass. Fifty percent of morbidly obese patients had LV diastolic filling abnormalities as assessed by the presence of greater than or equal to 2 abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in obese compared with control patients (1.16 +/- 0.26 vs 1.66 +/- 0.30, p less than 0.001). The peak velocity of early LV diastolic filling was significantly reduced in obese patients (75 +/- 15 vs 98 +/- 19 cm/s, p less than 0.001). The atrial contribution to stroke velocity as assessed by the time-velocity integral of late compared with total LV diastolic filling was significantly increased in obese patients (36 +/- 7 vs 27 +/- 4%, p less than 0.001). Obese patients had significantly increased LV mass (214 +/- 45 vs 138 +/- 37 g, p less than 0.001), even when corrected for body surface area (95 +/- 16 vs 76 +/- 16 g/m2, p less than 0.002). However, increased LV mass did not correlate with indexes of abnormal diastolic filling in obese patients. These data suggest that abnormalities of diastolic function occur frequently in asymptomatic morbidly obese patients and may represent a subclinical form of cardiomyopathy in the obese patient.

Angioscopic assessment of coronary lesions underlying thrombus.

This study examines the characteristics of coronary lesions in which thrombus is found as assessed by angioscopy before percutaneous transluminal coronary angioplasty in patients with various coronary syndromes. Our findings demonstrate that the plaque underlying intracoronary thrombus is usually yellow and/or disrupted, and support in vitro observations that lipid-rich plaques are highly thrombogenic and that disruption of these plaques is associated with in situ thrombosis.

Angioscopy of culprit coronary lesions in unstable angina pectoris and correlation of clinical presentation with plaque morphology.

This study demonstrates that plaque disruption and thrombus are absent in a considerable number of patients with unstable angina and that culprit lesion morphologies as assessed by angioscopy may differ among the various clinical subsets of patients. Although plaque disruption and thrombus undoubtedly play an important role in the pathogenesis of unstable angina, alternative mechanisms may be responsible for ischemia in some patients.

Age and history of cardiac disease as risk factors for cardiac complications after peripheral vascular surgery in diabetic patients.

OBJECTIVE: To examine the relationship of age and clinical factors to postoperative cardiovascular events in a cohort of diabetic patients undergoing peripheral vascular surgery. PATIENTS AND METHODS: In this cohort study, 316 diabetic patients were followed up prospectively after femoral-to-distal artery bypass surgery. The major end points of the study were all-cause mortality and cardiac morbidity (cardiac events defined as nonfatal myocardial infarction, unstable angina, and congestive heart failure). RESULTS: The overall postoperative cardiac event rate was 17.1% (54/316), with a 7.6% (24/316) rate of postoperative death or nonfatal myocardial infarction. Older diabetic patients (> or = 65 years) had a complication rate of 19.9% (43/216) compared with an 11.0% (11/100) complication rate in younger diabetic patients (< 65 years) (P = .02). Younger diabetic patients with a clinical history of coronary artery disease had an event rate of 18.2% (39/216) compared with an event rate of 2.4% (1/42) in younger diabetic patients without known cardiac disease (P = .02). In contrast, event rates were similar (20.7% [150/208] vs 18.2% [66/108]) in older diabetic patients with or without prior evidence of cardiac disease. CONCLUSION: Advanced age and clinical evidence of coronary artery disease are important determinants of postoperative outcome in diabetic patients undergoing peripheral vascular surgery.

Prospective evaluation of viable myocardium by quantitative dipyridamole-thallium-201 scintigraphy and radionuclide ventriculography.

Improvement of myocardial function is a major goal of coronary revascularization. Considerable interest remains in the preoperative identification of viable myocardium. We examined 26 consecutive patients with left ventricular dysfunction undergoing coronary artery bypass grafting. Serial dipyridamole-thallium imaging and radionuclide ventriculography was performed preoperatively and postoperatively. The relationship between preoperative and postoperative thallium perfusion and segmental wall motion was analyzed. The mean preoperative ejection fraction was 32 +/- 9 (21 to 51%) and increased to 41 +/- 12 (17 to 67%) postoperatively (p > 0.01). Seventy-seven percent of patients improved their global ejection fraction postoperatively by > 5%. Thallium perfusion improved postoperatively in 84% of reversible defects vs 63% of partially reversible defects and 35% of fixed defects. Segments with either reversible or partially reversible thallium defects showed an improved postoperative wall motion in 71% and 68%, respectively. Postoperative wall motion improved in 43% of fixed defects. Overall, 67% of hypokinetic segments showed improved postoperative wall motion while only 29% of akinetic or dyskinetic segments improved postoperatively. Preoperative thallium redistribution coupled with preserved wall motion was predictive of improvement in wall motion was predictive of improvement in wall motion postoperatively and indirectly indicates myocardial viability. However, 43% of fixed defects also showed improved postoperative wall motion. A significant improvement in global ejection fraction was found and could be predicted by a linear regression analysis utilizing clinical and thallium parameters.

Variability in the measurement of intracoronary ultrasound images: implications for the identification of atherosclerotic plaque regression.

BACKGROUND AND HYPOTHESIS: Serial coronary angiography cannot reliably detect the small changes in arterial dimensions. Measurement of arterial dimensions by intracoronary ultrasound (ICUS) may be a superior method to determine the extent of atherosclerotic burden since it directly images the diseased portion of the vessel. METHODS: To quantify inter- and intraobserver variability of ICUS measurements, 27 images of atherosclerotic coronary lesions were measured by two study physicians and repeated 14 days later. RESULTS: Interobserver correlation coefficients for external elastic lamina, lumen, and effective plaque area were 0.96, 0.99, and 0.91, respectively. Intraobserver correlation coefficients for external elastic lamina, lumen, and effective plaque area were 0.99, 0.99, and 0.97, respectively. To determine progression or regression in effective plaque area, a minimal difference of 2.77 mm2 (which represents a 23% change in plaque area) is needed. CONCLUSIONS: Direct visualization of the extent of atherosclerosis by ICUS can be accomplished with a low degree of inter- and intraobserver variability. ICUS may be a preferable alternative to angiography in atherosclerosis regression trials.

Diabetic cardiomyopathy.

Diabetes mellitus is associated with an excessive cardiovascular morbidity and mortality. Although one frequently associates cardiac dysfunction with enhanced coronary atherosclerosis in diabetic patients, evidence has accumulated for the existence of a specific "diabetic" cardiomyopathy. Abundant literature evidence supports the concept of myocardial dysfunction separate from epicardial coronary disease in diabetic individuals. The relationship of myocardial dysfunction to the type, duration, and treatment of diabetes awaits further delineation. The relative pathogenic significance of the multiple factors that may alter myocardial performance in diabetic patients similarly awaits further elucidation.

Severity of coronary artery disease in young patients with insulin-dependent diabetes mellitus.

Cardiovascular events remain a leading cause of morbidity and mortality in patients with juvenile-onset, insulin-dependent diabetes mellitus. To examine the extent and severity of the atherosclerotic lesions underlying this excess morbidity and mortality, clinical and angiographic findings were examined in 32 patients with insulin-dependent diabetes and in 31 nondiabetic patients, matched for age and symptoms, undergoing elective cardiac catheterization for evaluation of coronary artery disease. With respect to the individuals without diabetes, patients with insulin-dependent diabetes were significantly more likely to have severe narrowings, to have them in all three major coronary arteries, and to have them in distal segments. Severe narrowing of multiple vessels was significantly more common in men than in women and in individuals with hypercholesterolemia. We conclude that the high risk of cardiovascular events observed in young patients with insulin-dependent diabetes is secondary to advanced atherosclerotic lesions in coronary arteries. Involvement of distal segments of coronary arteries make these patients frequently unsuitable for bypass grafts.

Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: assessment by dipyridamole thallium-201 scintigraphy.

We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus.

Types of anesthesia and cardiovascular outcomes in patients with congestive heart failure undergoing vascular surgery.

BACKGROUND. Whether regional anesthesia is preferable to general anesthesia for patients with congestive heart failure (CHF) undergoing noncardiac surgery remains controversial. The purpose of this study was to determine whether anesthetic technique affects postoperative cardiac outcome in patients with CHF; we hypothesized that cardiac outcomes would be superior with regional anesthesia compared with general anesthesia. DESIGN. 106 patients with prior or persistent CHF, undergoing femoral to distal artery bypass surgery, were randomized to general anesthesia (29 patients) or regional anesthesia (epidural, 42 patients, or spinal anesthesia, 35 patients). The primary end point was death or adverse cardiac events (myocardial infarction, unstable angina, or CHF). RESULTS. There was no statistically significant difference between groups in incidence of combined cardiac events, death, myocardial infarction, death or myocardial infarction combined, unstable angina, or CHF. CONCLUSION. Although larger studies are required to establish equivalence of the anesthetic strategies, this large single center study preliminarily indicates that regional anesthesia may not be superior to general anesthesia in patients with heart failure undergoing femoral to distal artery bypass surgery. (c)1999 by CHF, Inc.

Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia.

BACKGROUND: Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease. METHODS: Four hundred twenty-three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure. RESULTS: Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was -1.6% (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia. CONCLUSIONS: The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery.