Clinical characteristics of patients with premature lower extremity atherosclerosis associated with familial early cardiovascular disease and/or cancer.

AIM: In the past decade we experienced a steady growth in the number of young smokers with severe premature lower extremity atherosclerosis (PLEA) and high frequency of familial cardiovascular disease (Fam CVD). The widely used Framingham risk score does not include Fam CVD among predictors of incident CVD. METHODS: We studied 370 patients younger than 55 with severe PLEA (45% females, 96% smokers) treated between 1998 and 2004. Overall, 312 (85%) patients reported a positive history of Fam CVD; 217 (59%) had family history of premature CVD (FamP-CVD), and 29% had history of early malignancies in family members <60 years (Fam Mal <60). RESULTS: Patients with FamP-CVD compared to those without FamP-CVD had similar prevalence of traditional risk factors, and concentrations of metabolic and inflammatory parameters, however had greater prevalence of clinical coronary artery disease (P=0.03), cerebrovascular disease (P=or<0.01) or both (P<0.01). Patients with both FamP-CVD and Fam Mal <60 (n=58) when compared to those with neither (n=92), had greater frequency of dyslipidemia (P=0.02) and coronary revascularizations (P=0.02). Patients with Fam P-CVD had 3-fold higher odds of prevalent CVD compared to those without Fam P-CVD. This association was independent of demographic and cardiovascular risks. CONCLUSIONS: In patients with PLEA, familial premature CVD may predict early clinical manifestations of systemic atherosclerosis, independently of traditional risk factors. Patients with family history of early malignancies had similar clinical characteristics, including prevalence of CVD.

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.

Management of ischemic nephropathy: dialysis-free survival after surgical repair.

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.

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 1x:x1 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 beta-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.

Perioperative cardiovascular morbidity in patients with coronary artery disease undergoing vascular surgery after percutaneous transluminal coronary angioplasty.

OBJECTIVE: Patients with coronary artery disease (CAD) who undergo noncardiac surgery are at increased risk for perioperative myocardial infarction (PMI). Undergoing successful coronary artery bypass grafting (CABG) before such surgery has been shown to decrease perioperative cardiac morbidity and mortality. Percutaneous transluminal coronary angioplasty (PTCA) is an alternative treatment for these patients. Perioperative cardiac morbidity in patients with CAD who underwent PTCA before their vascular surgery was reviewed. SETTING: A tertiary care referral center for patients with cardiovascular heart disease. PARTICIPANTS: Review of vascular surgery database for patients who underwent vascular surgery preceded by PTCA between 1984 and 1995. Patients were excluded if they had a history of CABG within 2 years of surgery, had PTCA more than 18 months before surgery, or had incomplete data. MEASUREMENTS: Data were collected concerning cardiac history, left ventricular (LV) function, perioperative cardiac morbidity (angina, MI, congestive heart failure [CHF], and arrhythmias). MAIN RESULTS: Of 194 patients who underwent aortic abdominal surgery, carotid endarterectomy (CEA), or peripheral vascular surgery preceded by PTCA, 104 (54%) had a previous MI. Twenty-six patients (13.4%) had perioperative cardiac morbidity. Only one patient had an MI (0.5%; 95% confidence interval [CI], 0.0 to 2.8), whereas one patient died of CHF followed by multisystem organ failure (0.5%). The median interval between PTCA and surgery was 11 days (interquartile range, [IQR] 3 to 49 days). Patients who developed perioperative cardiac morbidity were older than those who did not (p = 0.02). Patients who had a history of CABG (before PTCA) had a higher incidence of postoperative angina (p = 0.04). The degree of preoperative LV dysfunction was linearly related to the incidence of new postoperative CHF (p = 0.01). Arrhythmias were more common in patients undergoing abdominal vascular surgery (17.9%) than in those undergoing CEA (2.5%; p = 0.03) or peripheral vascular surgery (5.2%; p = 0.02). CONCLUSION: High-risk cardiac patients undergoing vascular surgery who have had PTCA performed up to 18 months preoperatively have a low incidence of perioperative cardiac morbidity. Prophylactic PTCA may be beneficial in patients with CAD who are at high risk for perioperative cardiac complications.

Ischemic liver dysfunction after elective repair of infrarenal aortic aneurysm: incidence and outcome.

OBJECTIVE: To assess the frequency of early postoperative liver dysfunction in patients undergoing elective infrarenal aortic aneurysm repair, their hospital course, and outcome. DESIGN: A retrospective case-control study. SETTING: A single tertiary referral center. PARTICIPANTS: A review of medical records of 942 consecutive asymptomatic patients with normal preoperative liver function test results who had elective infrarenal aortic aneurysm repair with infrarenal aortic cross-clamping. The authors selected all patients who had an acute increase in serum hepatic enzyme levels (minimum fivefold increase in aspartate aminotransferase [AST] and twofold increase in lactate dehydrogenase [LDH] levels) within the first 7 perioperative days (study patients). The control group consisted of 42 patients with normal postoperative liver function test results, matched by age, sex, and year of surgery to study patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Aortic cross-clamping times, lowest intraoperative blood pressure, duration of hypotension (systolic blood pressure < or = 95 mmHg), lowest intraoperative base deficit, and estimated blood loss were compared between control and study patients. The study also analyzed perioperative metabolic, hemostatic, hepatic, and renal function variables; the intraoperative course; postoperative complications; and inhospital outcome. Fourteen of 942 patients (1.5%) comprised a study group. In 11 patients (1.2%), AST and LDH levels moderately increased, and three patients (0.3%) developed changes consistent with a diagnosis of acute ischemic hepatitis (AIH). In all patients, the serum liver enzyme levels peaked between 24 and 72 postoperative hours. Three patients with AIH developed concomitant acute renal failure; one had associated disseminated intravascular coagulation (DIC) and died. Of 11 patients with moderate increases, one subsequently developed multisystem organ failure and died. The overall in-hospital mortality rate for patients with postoperative liver dysfunction was 14% (2/14) and for the control group it was 2.3% (1/42). The duration of hypotension and metabolic acidosis were more pronounced in patients who postoperatively developed liver dysfunction (both p < 0.001); however, study and control patients did not differ in the duration of aortic cross-clamping, lowest intraoperative blood pressure, or estimated blood loss. CONCLUSION: Liver enzyme levels acutely increased in 1.5% of patients after elective infrarenal aortic aneurysm repair with infrarenal cross-clamping. In patients with moderately elevated serum liver enzyme levels, postoperative recovery was relatively uncomplicated, whereas all three patients with AIH developed acute renal failure and had a more complicated postoperative course. Those with postoperative liver dysfunction had a longer duration of intraoperative hypotension and more pronounced metabolic acidosis.

Susceptibilities of Mycobacterium malmoense determined at the growth optimum pH (pH 6.0).

SETTING: Pulmonary disease caused by Mycobacterium malmoense is increasing. Conventional in vitro antimicrobial susceptibilities correlate poorly with response to treatment for this organism. Radiometrically determined minimum inhibitory concentrations (MICs) allow quantitative susceptibility testing for non-tuberculous mycobacteria. The M. avium complex (MAC) has been investigated extensively with this approach, and clear interpretative criteria have been established at pH 6.8. However, there has been little work with the acidophilic M. malmoense, which grows poorly at pH 6.8. OBJECTIVE: To determine whether MICs at pH 6.0 provide results compatible with the interpretative criteria established for the MAC. DESIGN: MICs were performed in Middlebrook PZA medium (pH 6.0) and 7H12 medium (pH 6.8) for ten strains of M. malmoense. RESULTS: MICs can be determined at pH 6.0 for M. malmoense using the criteria adopted for the M. avium complex. CONCLUSION: The low optimal pH of M. malmoense suits this organism for growth in acid conditions. As with MAC, M. malmoense multiplies within macrophages in vivo, and MICs determined at pH 6.0 may reflect in vivo activity. The combination of radiometric MIC testing at optimal growth pH and interpretation based on pharmacokinetic parameters may be helpful in designing therapeutic regimens.

Disseminated intravascular coagulation associated with acute ischemic hepatitis after elective aortic aneurysm repair: comparative analysis of 10 cases.

OBJECTIVE: To assess the characteristics of patients with perioperative disseminated intravascular coagulation (DIC) and acute ischemic hepatitis after elective aortic aneurysm repair (AAR). DESIGN: A retrospective case-control study. SETTING: A single tertiary referral center. PARTICIPANTS: Between 1982 and 1993, 1966 patients underwent elective AAR. Of these, 10 patients (eight with abdominal and two with thoracoabdominal aneurysms) developed DIC and acute elevation of serum transaminases consistent with acute ischemic hepatitis during or shortly after surgery. The control group included 30 patients matched by age, sex, year of surgery, and aneurysm type and size. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: None of the patients in either group had preoperative hemostatic abnormalities or other causes for DIC. There was no difference between the two groups in the duration of aortic cross-clamping. In all study patients, severe coagulopathy or systemic hypotension developed after the aortic cross-clamp was released. This resulted in significantly increased surgery time after unclamping (p < 0.001), and increased estimated blood loss (p < 0.001). DIC developed within 24 hours, and mean concentrations of aspartate transaminase (4,021 +/- 3,579 IU/L) and lactate dehydrogenase (4,332 +/- 2,903 IU/L) peaked on the second postoperative day. Nine (90%) of the study patients required repeat operations (seven for bleeding), and all of them died; the median survival time was 6 days (mean, 8.3 +/- 8.2 days). Only one patient in the control group needed a repeat operation. Liver infarction or necrosis was seen in all seven patients who underwent autopsy or biopsy. CONCLUSIONS: The combination of DIC and acute ischemic hepatitis ("hepatohemorrhagic syndrome") rarely occurs after elective AAR and is associated with a very high mortality rate. DIC was temporally related to the release of the aortic cross-clamp. The cause-effect relationship of this rare syndrome cannot be explained by operative course before the release of the aortic cross-clamp.

Lower extremity arterial occlusions in young patients with Crohn's colitis and premature atherosclerosis: report of six cases.

Arterial occlusive disease (AOD) which is rarely described in patients with inflammatory bowel disease, is mainly associated with Crohn's disease (CD), and its etiology and natural course are unknown. We studied six patients (five women, one man) with CD and major lower extremity AOD who were treated at the Cleveland Clinic between 1985 and 1994. These were relatively young patients (age range 24-48 years) with steroid-dependent Crohn' colitis. On their presentation, five had acute onset of severe ischemic symptoms ("blue toe" syndrome in three) and one had rapid progression of claudication. All the patients had active CD and/or prior extensive bowel resections, and had no evidence of extraintestinal manifestation. Cardiovascular risk factors were smoking (n = 5), dyslipidemia (n = 3), family history of coronary artery disease (n = 3), premature menopause (n = 2), diabetes mellitus (n = 1). Arteriograms showed iliac artery involvement in all six patients and bilateral AOD in three. None of the patients had arteriographic or clinical signs of vasculitis. Five patients required arterial revascularizations, i.e., endovascular (n = 2), surgical (n = 2), and combined in one. Three patients had microscopic evidence of atherosclerosis. Lower extremity AOD in patients less than 50 yr of age and with CD may be partially related to premature atherosclerosis. Prospective screening for cardiovascular risk factors, subclinical disease, and hypercoagulability might be indicated in patients with active CD to prevent major arterial complications.

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.

Isolation and characterization of the fibrin intermediate arising from cleavage of one fibrinopeptide A from fibrinogen.

The thrombin-catalyzed cleavage of N-terminal fibrinopeptide A (FPA) from the two Aalpha-chains of fibrinogen exposes aggregation sites with the critical sequence GPR located just behind FPA. It is well known that exposure of both GPR sites transforms fibrinogen into self-aggregating, fully coagulable alpha-fibrin monomers, but the fibrin precursor with one site exposed and one FPA intact has eluded description. The formation of this "alpha-profibrin" in the course of thrombin reactions and its distribution among both the aggregating and non-aggregating components of the reactions are characterized here by immunoprobing electrophoretic and gel chromatographic separations using monoclonal antibodies specific for FPA and for exposed GPR sites. These analyses show alpha-profibrin to be a non-aggregating derivative indistinguishable from fibrinogen in solutions that are rich in fibrinogen relative to dissolved fibrin. But alpha-profibrin forms soluble complexes with alpha-fibrin monomer under conditions in which it and fibrin predominate over fibrinogen. It was isolated as a complex with fibrin by gel chromatography of cryoprecipitates and then separated from the fibrin either by electrophoretic gel shifts induced with a peptide analog of the GPR aggregation site or by chromatographic gel shifts induced with monoclonal anti-FPA antibody. The weak aggregation of alpha-profibrin with itself and with fibrinogen conforms with prior indications that coupled interactions through the paired GPR sites on fibrin monomers are pivotal to their aggregation. It is suggested that alpha-profibrin may be a hypercoagulable fibrin precursor because it is converted to alpha-fibrin monomer faster than fibrinogen converts to monomer.

A prospective evaluation of atherosclerotic risk factors and hypercoagulability in young adults with premature lower extremity atherosclerosis.

PURPOSE: Fifty-one consecutive patients with premature lower extremity atherosclerosis were prospectively evaluated for atherogenic risk factors and primary or acquired hypercoagulability, which might contribute to early ischemia and revascularization failure. METHODS: Laboratory tests included plasma assays of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin antibodies, and (2) fibrinolytic activators and inhibitors at baseline and stimulated after 20 minutes of upper extremity venous occlusion. RESULTS: Forty-six (90%) of these 51 patients had laboratory abnormalities. One or more NAC deficiencies were found in 15 (30%) patients and included antithrombin III (n = 5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2). Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1 (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%) patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies, especially protein C deficiency, were associated with acute ischemia (p < 0.01), prior vascular intervention (p < 0.01), an increasing number of total vascular procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05). Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20 patients suggested that 80% of NAC deficiencies were acquired, but abnormalities persisted in 66% of patients with elevated PAI-1 and in 93% of those with elevated Lp(a). CONCLUSIONS: These data strongly support the hypothesis that the convergence of atherogenic risk factors and hypercoagulability play an important role in early ischemia and poor results reported for lower extremity vascular procedures in young adults.

Percutaneous transluminal angioplasty in adults less than 45 years of age with premature lower extremity atherosclerosis.

Despite poor results reported with conventional vascular bypasses in young adults with ischemia from premature lower extremity atherosclerosis (PLEA), little attention has been given to alternative revascularization techniques. This study evaluated 32 patients (21 males and 11 females) < 45 years of age with PLEA who underwent 53 primary percutaneous transluminal angioplasty (PTA) procedures for treatment of 46 ischemic limbs. A residual arterial stenosis < 30% was achieved in 83% of PTA sites. Mean degree of stenosis decreased from 79.9% to 24.1% (p < 0.0001). Clinical improvement in ischemic symptoms was obtained in 39 (85%) limbs. Hemodynamic improvement was achieved in 31 (70%) of 40 limbs as documented by ankle/brachial indices. All criteria for early clinical success were met in 70%. Another 13% met all criteria except that the residual stenosis was < 50%. Hematoma and early restenosis were reported in two patients each. Mean follow-up was 27.3 months (range 1 to 84 months). Cumulative patency by life-table analysis was 81% at 1 year, 77% at 2 years, and 71% at 3 years. Thirteen (41%) patients required secondary PTA or bypass; 85% were performed within 1 year. Two patients had adjunctive bypasses; six (19%) were performed after PTA failure. Only one (3%) patient required major amputation. Neither cardiovascular risk factors, treatment indication, location of the diseased arterial segment, nor quality of distal runoff vessels predicted the need for secondary PTA or surgical procedures. PTA of the proximal arteries in young patients with PLEA is an effective primary revascularization technique with results comparable to those of conventional operative revascularization procedures.

Massive lower extremity arterial thrombosis and acute hepatic insufficiency in a young adult with premature atherosclerosis associated with hyperlipoprotein(a)emia and antiphospholipid syndrome. A case report.

The authors describe a healthy young male smoker with familial history of recurrent thromboembolism who presented with severe, rapidly progressive lower limb ischemia and abnormal results from liver function tests. An arteriogram of the lower extremities showed bilateral infrainguinal atherosclerotic arterial occlusions. The laboratory findings, in addition to abnormal liver function findings, included moderately elevated antiphospholipid antibodies and hemostatic abnormalities involving elevated fibrinogen, lipoprotein (a) levels, and deficient fibrinolysis. He underwent bilateral femoral thrombectomy, which was followed by a meticulous anticoagulation, and had gradual improvement of ischemic symptoms and liver functions. This is, to their knowledge, the first reported case in the English literature of premature lower extremity atherosclerosis and antiphospholipid syndrome associated with elevated lipoprotein (a) levels and documented complex hemostatic abnormalities contributing to systemic thrombosis.

Diffuse arterial thrombosis in a young man with elevated lipoprotein(a) and minimal atherosclerosis.

An increased incidence of premature atherosclerotic arterial occlusive disease was recently reported in young adults. This condition is characterized by early occurrence of severe symptoms, lower incidence of typical cardiovascular risk factors for atherosclerosis, different natural course of arterial disease vis-a-vis older population, and poor outcome of a standard treatment. This report describes a young man with aggressive arterial occlusive disease in the lower extremities and symptom-free occlusions of coronary and renal arteries in association with high levels of lipoprotein(a). Microscopic early atherosclerotic changes were noted in the occluded arteries of the amputated leg. Premature atherosclerotic arterial occlusive disease in young adults has different clinical and pathological patterns, necessitating a different approach for evaluation and treatment.

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).

Hypercoagulable states as an evolving risk for spontaneous venous and arterial thrombosis.

This study of 49 patients with spontaneous venous and arterial thrombosis identified 27 with hypercoagulable states: 13 had only venous thrombosis (VT), six had episodes of VT followed by arterial thrombosis (AT) and eight had AT only. All 27 patients were less than 42 years of age; 22 had specific natural anticoagulant or fibrinolytic deficiencies: antithrombin III (nine patients), protein C (eight patients), protein S (three patients), heparin cofactor II (two patients), tissue plasminogen activator release (one patient) and mixed antithrombin III and protein S (one patient). The remaining five patients had recurrent thrombotic events associated with resistance to heparin anticoagulation, but no established laboratory diagnosis. Clotting complications included recurrent VT, pulmonary embolism, multiple failed arterial procedures and lower extremity amputation. The remaining 22 patients (mean age of 53 years, range of 46 to 63 years), 12 with VT and ten with AT, did not have laboratory evidence of hypercoagulability and none had recurrent vascular occlusions. All these patients were successfully treated by conventional therapy without any additional thrombotic events during the follow-up period. Young adults with spontaneous thrombotic events should be screened for possible hypercoagulable states. Additionally, these young patients need further evaluation and treatment of cardiovascular risk factors. Those with premature atherosclerosis have an especially poor prognosis despite surgical intervention and anticoagulant therapy.

Rare presentation of anastomotic iliac artery false aneurysm: rupture with formation of ilio-iliac arteriovenous fistula.

A rare complication of aortoiliac bypass procedure resulting in the formation of an acute ilio-iliac arteriovenous fistula was presented. The latter was a first manifestation of anastomotic iliac pseudoaneurysm. This is only the second such case reported in the English literature. Iliac anastomotic pseudoaneurysm although rarely detected, is a potentially lethal complication that has to be repaired close to the time of its detection.

Rapid broth macrodilution method for determination of MICs for Mycobacterium avium isolates.

A multicenter study was done to investigate the accuracy and reproducibility of a method for determining the MICs of antimicrobial agents against the Mycobacterium avium complex in 7H12 broth with the BACTEC system. In phase I, with eight drugs and 10 strains, intralaboratory reproducibility was 95.7 to 100%, allowing a 1-dilution difference upon repeat testing. The results of phase II testing with 41 additional strains were consistent with those obtained in phase I, with good interlaboratory reproducibility. The radiometric method was validated by sampling and plating of the same broth cultures and determining, by the number of CFU per milliliter, the lowest drug concentration that inhibited more than 99% of the initial bacterial population. Three test concentrations of each drug and the tentative interpretation of results are proposed. Radiometric MIC determination has the potential to become the method of choice for clinical microbiology laboratories and evaluation of new agents for the treatment of M. avium infections, both pulmonary and disseminated.