Gilbert J. L'Italien

Association of the Metabolic Syndrome With History of Myocardial Infarction and Stroke in the Third National Health and Nutrition Examination Survey

Background—The combination of cardiovascular risk factors known as the metabolic syndrome is receiving increased attention from physicians, but data on the syndrome’s association with morbidity are limited. Methods and Results—Applying National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria, we evaluated 10 357 NHANES III subjects for the 5 component conditions of the metabolic syndrome: insulin resistance, abdominal obesity based on waist circumference, hypertriglyceridemia, low HDL cholesterol (HDL-C), and hypertension, as well as the full syndrome, defined as at least 3 of the 5 conditions. Logistic regression was used to estimate the cross-sectional association of the syndrome and each of its 5 component conditions separately with history of myocardial infarction (MI), stroke, and either MI or stroke (MI/stroke). Models were adjusted for age, sex, race, and cigarette smoking. The metabolic syndrome was significantly related in multivariate analysis to MI (OR, 2.01; 95% CI, 1.53 to 2.64), stroke (OR, 2.16; 95% CI, 1.48 to 3.16), and MI/stroke (OR, 2.05; 95% CI, 1.64 to 2.57). The syndrome was significantly associated with MI/stroke in both women and men. Among the component conditions, insulin resistance (OR, 1.30; 95% CI, 1.03 to 1.66), low HDL-C (OR, 1.35; 95% CI, 1.05 to 1.74), hypertension (OR, 1.44; 95% CI, 1.00 to 2.08), and hypertriglyceridemia (OR, 1.66; 95% CI=1.20 to 2.30) were independently and significantly related to MI/stroke. Conclusions—These results indicate a strong, consistent relationship of the metabolic syndrome with prevalent MI and stroke.

Effect of compliance mismatch on vascular graft patency

The hypothesis that a mismatch in compliance between a vascular graft and its host artery is detrimental to graft patency was tested by implanting paired arterial autografts, prepared with differential glutaraldehyde fixation of carotid arteries in the femoral arteries of dogs. These grafts differed only in circumferential compliance: they were 100% (compliant) vs. 40% (stiff) as compliant as the host artery. Their flow surfaces were equivalent, as determined by physicochemical measurements and scanning electron microscopy; both lacked viable cells, as determined by in vitro cell culture. In 14 dogs, eight stiff and two compliant grafts became occluded within 3 months, the latter doing so within 24 hours after their contralateral counterparts. Cumulative patencies were 85% and 37% for compliant and stiff grafts, respectively (p less than 0.05) and 100% and 43%, excluding the two dogs with bilateral graft failures (p less than 0.01). We conclude that even with near optimal flow surfaces, compliance mismatch is deleterious to graft patency.

Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair

PURPOSE This report summarizes our experience with epidural cooling (EC) to achieve regional spinal cord hypothermia and thereby decrease the risk of spinal cord ischemic injury during the course of descending thoracic aneurysm (TA) and thoracoabdominal aneurysm (TAA) repair. METHODS During the interval July 1993 to Dec. 1995, 70 patients underwent TA (n = 9, 13%) or TAA (n = 61) (type I, 24 [34%], type II, 11 [15%], type III, 26 [37%]) repair using the EC technique. The latter was accomplished by continuous infusion of normal saline (4 degrees C) into a T11-12 epidural catheter; an intrathecal catheter was placed at the L3-4 level for monitoring of cerebrospinal fluid temperature (CSFT) and pressure (CSFP). All operations (one exception, atriofemoral bypass) were performed with the clamp-and-sew technique, and 50% of patients had preservation of intercostal vessels at proximal or distal anastomoses (30%) or by separate inclusion button (20%). Neurologic outcome was compared with a published predictive model for the incidence of neurologic deficits after TAA repair and with a matched (Type IV excluded) consecutive, control group (n = 55) who underwent TAA repair in the period 1990 to 1993 before use of EC. RESULTS EC was successful in all patients, with a 1442 +/- 718 ml mean (range, 200 to 3500 ml) volume of infusate; CSFT was reduced to a mean of 24 degrees +/- 3 degrees C during aortic cross-clamping with maintenance of core temperature of 34 degrees +/- 0.8 +/- C. Mean CSFP increased from baseline values of 13 +/- 8 mm Hg to 31 +/- 6 mm Hg during cross-clamp. Seven patients (10%) died within 60 days of surgery, but all survived long enough for evaluation of neurologic deficits. The EC group and control group were well-matched with respect to mean age, incidence of acute presentations/aortic dissection/aneurysm rupture, TAA type distribution, and aortic cross-clamp times. Two lower extremity neurologic deficits (2.9%) were observed in the EC patients and 13 (23%) in the control group (p < 0.0001). Observed and predicted deficits in the EC patients were 2.9% and 20.0% (p = 0.001), and for the control group 23% and 17.8% (p = 0.48). In considering EC and control patients (n = 115), variables associated with postoperative neurologic deficit were prolonged (> 60 min) visceral aortic cross-clamp time (relative risk, 4.4; 95% CI, 1.2 to 16.5; p = 0.02) and lack of epidural cooling (relative risk, 9.8; 95% CI, 2 to 48; p = 0.005). CONCLUSION EC is a safe and effective technique to increase the ischemic tolerance of the spinal cord during TA or TAA repair. When used in conjunction with a clamp-and-sew technique and a strategy of selective intercostal reanastomosis, EC has significantly reduced the incidence of neurologic deficits after TAA repair.

Comparative early and late cardiac morbidity among patients requiring different vascular surgery procedures

PURPOSE The evaluation of coronary artery disease (CAD) in patients undergoing vascular surgery can provide information with respect to perioperative and long-term risk for CAD-related events. However, the extent to which the required surgical procedure itself imparts additional risk beyond that dictated by the presence of CAD determinants remains in question. The purpose of this study was to quantify the relative contributions of specific vascular procedures and CAD markers on perioperative and long-term cardiac risk. METHODS The study cohort comprised 547 patients undergoing vascular surgery from two medical centers who underwent clinical evaluation, dipyridamole thallium testing, and either aortic (n = 321), infrainguinal (n = 177), or carotid (n = 49) vascular surgery between 1984 and 1991. Perioperative and late cardiac risk of fatal or nonfatal myocardial infarction (MI) was compared for the three procedures before and after adjustment for the influence of comorbid factors. These adjusted estimates may be regarded as the component of risk because of type of surgery. RESULTS Perioperative MI occurred in 6% of patients undergoing aortic and carotid artery surgery, and in 13% of patients undergoing infrainguinal procedures (p = 0.019). Significant (p < 0.05) predictors of MI were history of angina, fixed and reversible dipyridamole thallium defects, and ischemic ST depression during testing. Although patients undergoing infrainguinal procedures exhibited more than twice the risk for perioperative MI compared with patients undergoing aortic surgery (relative risk: 2.4[1.2 to 4.5, p = 0.008]), this value was reduced to insignificant levels (1.6[0.8 to 3.2, p = 0.189]) after adjustment for comorbid factors. There was little change in comparative risk between carotid artery and aortic procedures before (1.0[0.3 to 3.6, p = 0.95]) or after (0.6[0.2 to 2.3, p = 0.4]) covariate adjustment. The 4-year cumulative event-free survival rate was 90% +/- 2% for aortic, 74% +/- 5% for infrainguinal, and 78% +/- 7% for carotid artery procedures (p = 0.0001). Predictors of late MI included history of angina, congestive heart failure, diabetes, fixed dipyridamole thallium defects, and perioperative MI. Patients undergoing infrainguinal procedures exhibited a threefold greater risk for late events compared with patients undergoing aortic procedures (relative risk: 3.0[1.8 to 5.1, p = 0.005]), but this value was reduced to 1.3(0.8 to 2.3, p = 0.32) after adjustment. Long-term risk among patients undergoing carotid artery surgery was less dramatically altered by risk factor adjustment. CONCLUSION In current practice, among patients referred for dipyridamole testing before operation, observed differences in cardiac risk of vascular surgery procedures may be primarily attributable to readily identifiable CAD risk factors rather than to the specific type of vascular surgery. Thus the cardiac and diabetic status of patients should be given careful consideration whenever possible, regardless of surgical procedure to be performed.

Renal failure after thoracoabdominal aortic surgery

PURPOSE Renal failure remains a common and morbid complication after complex aortic surgery. This study was performed to identify perioperative factors that contribute to postoperative renal failure. METHODS The perioperative outcomes of 183 patients who underwent thoracoabdominal aortic surgery with supraceliac clamping were reviewed. During the interval from Jan. 1987 to Nov. 1996, thoracoabdominal aneurysm repair was performed in 154 patients (type I, 49 patients [27%]; type II, 21 patients [11.5%]; type III, 55 patients [30%]; type IV, 29 patients [16%]), suprarenal abdominal aortic aneurysm repair in 17 patients (9%), and visceral/renal revascularization procedures in 12 patients (6.5%). Intraoperative management included thoracoabdominal aortic exposure and clamp-and-sew technique with renal artery cold perfusion whenever the renal arteries were accessible (79% of cases). RESULTS Relevant clinical features included preoperative hypertension (85%), diabetes mellitus (8%), single functioning kidney (10%), recent intravenous contrast injection (34%), renal insufficiency (creatinine level greater than 1.5 mg/dl; 24%), and emergent operation (19%). Acute renal failure, defined as both a doubling of serum creatinine level and an absolute value greater than 3.0 mg/dl, occurred in 21 patients (11.5%), of whom five required hemodialysis (2.7%). Variables associated with this complication included a preoperative creatinine level greater than 1.5 mg/dl (p = 0.004) and a total cross-clamp time greater than 100 minutes (p = 0.035). The operative mortality risk (within 30 days; 8%) was significantly increased with renal failure (odds ratio, 9.2; 95% confidence interval, 2.6 to 33; p < 0.005). CONCLUSIONS Renal failure, although uncommon in contemporary practice, greatly increases the risk of early death after thoracoabdominal aortic surgery. The overall incidence of renal failure and dialysis requirement in the present series compare favorably with those reported using other operative techniques, specifically partial left heart bypass and distal aortic perfusion. These data suggest that patients who have preoperative renal insufficiency are prone to postoperative renal failure. Furthermore, regional hypothermic perfusion and minimal clamp times are important elements in the prevention of renal failure after thoracoabdominal aortic surgery.

Magnetic resonance angiography in the management of lower extremity arterial occlusive disease: a prospective study.

PURPOSE We conducted a prospective study to clarify the clinical utility of magnetic resonance angiography (MRA) in the treatment of patients with lower extremity arterial occlusive disease. METHODS During the interval of September 1993 through March 1995, 79 patients (43% claudicants, 57% limb-threatening ischemia) were studied with both MRA and contrast arteriography (ANGIO) and underwent intervention with either balloon angioplasty (9%), surgical inflow (28%), or outflow (63%) procedures. MRA and ANGIO were interpreted by separate blinded vascular radiologists, and arterial segments from the pelvis to the foot were graded as normal or with increasing degrees of mild (25% to 50%), moderate (51% to 75%), or severe (75% to 99%) stenosis or occlusion. Treatment plans were formulated by the attending surgeon and were based initially on hemodynamic, clinical, and MRA data and thereafter with ANGIO. Additional study surgeons formulated independent and specific treatment plans based on MRA or ANGIO alone. Indexes of agreement (beyond chance) for arterial segments depicted by MRA and ANGIO were assessed (kappa value), and treatment plans formulated were compared (chi-square). RESULTS Precise agreement (%) and the percent of major discrepancies (segment classified as normal/mild stenosis on one study and severe stenosis/occlusion on the other) between MRA and ANGIO for respective arterial segments was as follows: common and external iliacs (n = 256) 77/3.5; superficial femoral and above-knee popliteal (n = 255) 73/6.7; below-knee popliteal (n = 131) 84/3.8; infrapopliteal runoff vessels (n = 864) 74/12.4; pedal vessels (n = 111) 69/19.8 Kappa values indicated moderate agreement (between MRA and ANGIO) beyond chance for all arterial segments. Treatment plans formulated by the attending surgeon, the MRA surgeon, and the ANGIO surgeon agreed in more than 85% of cases. Inability of MRA to assess the significance of inflow disease and inadequate detail of tibial/pedal vessels were the principal deficiencies of MRA in those cases where it was considered an inadequate examination. CONCLUSION These findings suggest MRA and ANGIO are nearly equivalent examinations in the demonstration of infrainguinal vascular anatomy. MRA is an adequate preoperative imaging study (and may replace ANGIO), particularly in those circumstances when the risk of ANGIO is increased or when clinical and hemodynamic evaluation predict the likelihood of straightforward aortofemoral or femoral-popliteal reconstruction.

Injury markers predict time to dementia in subjects with MCI and amyloid pathology

Objectives: Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology. Methods: We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimers Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of β-amyloid1−42 (Aβ1–42) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models. Results: We included 110 subjects with MCI with abnormal CSF Aβ1–42 and a mean MMSE score of 26.3 ± 2.8. During a mean follow-up of 2.2 ± 1.0 (range 0.4–5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1–4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3–9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1–5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0–55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score. Conclusions: In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.

Renal artery reconstruction for the preservation of renal function

PURPOSE We reviewed a 13-year experience with an emphasis on long-term survival and renal function response when renal artery reconstruction (RAR) was performed primarily for the preservation or restoration of renal function in patients who had atherosclerotic renovascular disease. METHODS From January 1, 1980, to June 30, 1993, 139 patients underwent RAR for renal function salvage and were retrospectively reviewed. Inclusion criteria were either preoperative serum creatinine level > 2.0 mg/dl (67% of patients) or RAR to the entire functioning renal mass irrespective of baseline renal function. Patient survival was calculated by life-table methods. Cox regression analysis was used to determine relative risk (RR) estimates for the late outcomes of continued deterioration of renal function and late survival after RAR. A logistic regression model was used to evaluate variables associated with perioperative complications. RESULTS Clinical characteristics of the cohort were notable for advanced cardiac (history of congestive heart failure, 27%; angina, 22%; previous myocardial infarction, 19%) and renal disease (serum creatinine level < 2.0 mg/dl, 33%; 2.0 mg/dl to 3.0 mg/dl, 40%, > 3.0 mg/dl, 27%). Cardiac disease was the principle cause of early (6 of 11 operative deaths) and late death. Operative management consisted of aortorenal bypass in 47%, extraanatomic bypass in 45%, and endarterectomy in 8%; 45% of patients required combined aortic and RAR. The operative mortality rate was 8%; significant perioperative renal dysfunction occurred in 10%. Major operative morbidity was associated with increasing azotemia (RR = 2.1; p = 0.001; 95% confidence interval [CI], 1.3 to 4.7 for each 1.0 mg/dl increase in baseline creatinine level). Of those patients who had a baseline creatinine level > or = 2.0 mg/dl, 54% had > or = 20% reduction in creatinine level after RAR. Late follow-up data were available for 87% of operative survivors at a mean duration of 4 years (range, 6 weeks to 12.6 years). Actuarial survival at 5 years was 52% +/- 5%. Continued deterioration in renal function occurred in 24% of patients who survived operation, and eventual dialysis was required in 15%. Deterioration of renal function after RAR was associated with increasing levels of preoperative creatinine (RR = 1.6; 95% CI, 1.2 to 1.8; p = 0.001 for each 1.0 mg/dl increment in baseline creatinine level), and inversely related to early postoperative improvement in creatinine level (RR = 0.41; 95% CI, 0.2 to 0.9; p = 0.04). CONCLUSIONS Intervention before major deterioration in renal function and an aggressive posture toward the frequently associated coronary artery disease are necessary to improve long-term results when RAR is performed for renal function salvage.

Epidemiology and natural history of hepatitis C virus infection

Hepatitis C virus (HCV) affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma. Globally, at least one third of hepatocellular carcinoma cases are attributed to HCV infection, and 350000 people died from HCV related diseases per year. There is a great geographical variation of HCV infection globally, with risk factors for the HCV infection differing in various countries. The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations. A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma, and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma. However, prospective cohorts comprising individuals with HCV infection are still uncommon. The risk evaluation of viral load elevation and associated liver disease/cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years. Most of them have acquired HCV infection through iatrogenic transmission routes. As the participants in the REVEAL-HCV study rarely receive antiviral therapies, it provides a unique opportunity to study the natural history of chronic HCV infection. In this review, the prevalence, risk factors and natural history of HCV infection are comprehensively reviewed. The study cohort, data collection, and findings on liver disease progression of the REVEAL-HCV study are described.

The incidence of diabetes in atypical antipsychotic users differs according to agent—results from a multisite epidemiologic study†

The purpose of this study was to examine the association between atypical antipsychotics, including the newer agents, aripiprazole and ziprasidone, and newly treated diabetes, using the largest post‐marketing cohort of patients exposed to these newer treatments that has been studied to date.