Lipoprotein (a): Relationship to vascular disease in dialysis and renal transplantion

Summary: Serum lipids and lipoprotein (a) concentrations were measured in 91 renal transplant and 60 dialysis patients and correlations sought with clinically evident vascular disease. Serum lipoprotein (a) concentrations were greater than 300 mg/L in 24% of the renal transplant recipients and 40% of the dialysis patients. In the renal transplant recipients, low high density lipoprotein (HDL) cholesterol ( P <0.05) and high total cholesterol to HDL cholesterol ratio ( P <0.01) were more strongly associated with the presence of vascular disease than was elevated lipoprotein (a). In the dialysis patients, a low serum albumin ( P <0.05) and low serum creatinine ( P <0.001), indicative of a poor nutritional state, were associated with the presence of vascular disease. A high total serum cholesterol to HDL cholesterol ratio ( P <0.05) was indicative of ischaemic heart disease, and high total serum cholesterol ( P <0.01) and low density lipoprotein (LDL) cholesterol ( P <0.01) of cerebrovascular disease. In the subpopulation on CAPD, elevated lipoprotein (a) levels were associated with cerebrovascular disease ( P <0.01). the present study demonstrates that an elevation in serum lipoprotein (a) concentration is not as strongly associated with the presence of vascular disease in patients with end-stage renal failure as are the total serum cholesterol, HDL and LDL cholesterol and the ratio of total cholesterol to HDL cholesterol.     

Lipoprotein (a): A risk factor for peripheral vascular disease

Lipoprotein (a) [Lp(a)] is a serum protein that has been reported to be predictive of complications from coronary and cerebrovascular atherosclerotic disease. This study was designed to compare plasma levels of Lp(a) in 100 white male patients with and without peripheral vascular disease (PVD) and to determine the role of Lp(a) as a risk factor for PVD independent of known risk factors such as cigarette smoking (CIG), diabetes mellitus (DM), and coronary artery disease (CAD). Patients with PVD (mean age =67.6 years, n=50) had a statistically significant (p=0.04) elevation of Lp(a) (29.8±3.9 mg/dl) as compared to patients without PVD (20.0±2.9 mg/dl (mean age =68.3 years, n=50). Further analysis revealed that patients with PVD had a significantly higher incidence of CIG (86% vs. 68%,p=0.03), DM (34% vs. 14%,p=0.02), and CAD (52% vs. 30%,p=0.02) than those without PVD. However, there was no statistically significant difference in Lp(a) levels in patients with CIG or CAD compared to those without. Patients with DM had significantly (p=0.04) lower levels of Lp(a) (17.8±3.5 mg/dl) than those without DM (27.1±3.0 mg/dl). Stepwise regression analysis of these various risk factors for PVD revealed that Lp(a) was the strongest significant individual predictor for the presence of PVD (R ²=0.07) as compared to DM (R ²=0.05) and CIG (R ²=0.04). We conclude that there is a significant correlation of Lp(a) levels and the incidence of PVD, which is independent of other major risk factors for PVD.Supported by grants NIH NRSA F32HL0824501A1 to M.D.W. and NIH R29HL40305, RO1HL47345, and VA Merit Grant to B.E.S.Presented at the Sixth Annual Meeting of the Eastern Vascular Society, New York, N.Y., May 2, 1992.     

Amputations in peripheral vascular occlusive disease

One hundred consecutive patients undergoing major lower extremity amputations were critically analyzed over a five year period. The results of surgical care and the degree of success of rehabilitation were determined. The number of patients with peripheral vascular occlusive disease who require major lower extremity amputations appears to be increasing and they continue to present a challenge to the surgeon.     

Axillofemoral bypass: a critical reappraisal of its role in the management of aortoiliac occlusive disease.

Two hundred twenty-four consecutive patients (361 graft limbs) who underwent bypass grafting with the USCI Sauvage filamentous velour Dacron arterial prosthesis for aortoiliac occlusive disease over the 9 year period 1970 to 1979 are reviewed. Eighty-four axillofemoral (23 percent of patients), 210 aortofemoral (47 percent of patients), and 67 femorofemoral grafts (30 percent of patients) had cumulative patency rates of 72.1, 91.1, and 86.4 percent, respectively. Experimental and clinical factors influencing the patency of axillofemoral grafts are discussed, and the concept of an improved porous Dacron prosthesis specific for the axillofemoral site is presented.     

Lipoprotein (a) in patients with aortic aneurysmal disease

OBJECTIVE: Lipoprotein (a) is an independent risk factor for atherosclerosis. Atherosclerotic degeneration is usually found in abdominal aortic aneurysms (AAAs), whereas thoracic aortic aneurysms (TAAs) caused by aortic dissection are not suggested to be linked pathogenetically to atherosclerosis. Lipoprotein (a) was analyzed in patients with AAA and TAA and in healthy individuals in relation to the extent of atherosclerosis. METHODS: Included in the case control study were patients with AAA (n = 75) and TAA with dissection (n = 39) and healthy control subjects (n = 43), for a total of 157 participants. Serum lipoprotein (a) was measured with nephelometry. Lipoprotein (a) levels were compared between age-matched and gender-matched paired samples of the three groups, and an association of lipoprotein (a), aortic aneurysm, and the extent of atherosclerosis was determined in multivariate analysis. RESULTS: Median lipoprotein (a) levels of patients with AAA and TAA and of control subjects were 18.9 mg/dL (interquartile range [IQR], <9.6 to 40.5), less than 9.6 mg/dL (IQR, <9.6 to 16.7), and less than 9.6 mg/dL (IQR, <9.6 to 16.3), respectively. Lipoprotein (a) was positively associated with the extent of atherosclerosis in patients and control subjects (P <.0001). Lipoprotein (a) levels of patients with AAA were significantly higher compared with patients with TAA (P <.0001) and control subjects (P <.0001). Multivariate analysis confirmed an independent association between lipoprotein (a) and AAA (P =.009). No significant differences of lipoprotein (a) were found between patients with TAA and control subjects (P =.3). CONCLUSION: The lipoprotein (a) serum level, an indicator of atherosclerosis, is significantly elevated in patients with abdominal aneurysms independently of cardiovascular risk factors and the extent of atherosclerosis. Patients with TAAs caused by dissection have lipoprotein (a) levels comparable with healthy individuals.     

Continuous wave (CW) and pulsed laser effects on vascular tissues and occlusive disease in vitro

Human arterial segments with occlusive defects and acute dog hearts were exposed, in vitro, to high-energy pulsed and continuous wave (CW) laser beams at argon (514 nm) and Nd-YAG (1,064 nm) wavelengths, using various pulse powers, durations and pulse repetition rates. The laser effects included vaporization of plaques in the arterial segments and penetration of the pericardial sac, evaporation of pericardial fluid, and discoloration of tissue with crater-like lesions in the impact zone, all as a result of vaporization of heart muscle tissues. The areas affected and depth of penetration depended on the wavelength, power, pulse duration, and mode of energy deposition. Focused nanosecond Nd-YAG laser pulses at repetition rates of 40-50 Hz caused ablation or vaporization of hard plaques and kidney stones in air and saline. Picosecond (mode-locked) argon laser pulses at repetition rates of 3.8 MHz--average power 6.5 W, peak power of 230 W--caused effective vaporization of hard plaques and kidney stones in air and saline. Picosecond argon laser pulses--average power 1 W, peak power 250 W--were not effective in vaporization. Transmission characteristics of the various types of laser pulses through fiber optic waveguides were determined. The energy and power density required to vaporize fatty and hard plaques and kidney stones were tabulated as a function of laser wavelength, pulse energy, duration, and repetition rates.     

Multilevel occlusive vascular disease presenting with gangrene

The medical records of all patients subjected to lower extremity amputations during a 3-year period were reviewed. It was shown that advanced age and the presence of multiple medical problems do not predispose to higher levels of limb loss. Although diabetic patients more frequently undergo amputation because of sepsis than their nondiabetic counterparts, the diabetic state was not found to be associated with a greater likelihood of above knee (AK) procedures. Prior arterial surgery was not shown to make AK amputation more likely, but it was disconcerting to note that limb salvage was not achieved in many individuals despite patent proximal inflow revascularization procedures. This initial study showed that several presumed risk factors were not predictors of amputation level. Those patients requiring AK amputations had a greater frequency of combined segment (aortoiliac and femoropopliteal) occlusive disease than those who had successful amputations at more distal levels. A follow-up study of 41 consecutive patients presenting with tissue loss due to combined segment occlusive disease was performed. Eighteen (Group I) underwent inflow procedures only, while 23 (Group II) also underwent distal revascularization. The groups were similar with respect to age, risk factors, extent of tissue loss and sepsis. At 1 year 10 (56%) Group I and only 3 (13%) Group II patients required major amputation (P = 0.01). Distal bypass, in addition to an inflow procedure, is recommended for those who present with tissue loss due to multilevel arterial occlusion.     

Minimum vascular occlusive force.

A mathematical analysis of the minimum occlusion force necessary to occlude small vessels based on the parametric influence of blood pressure, vessel diameter, clamp width, and vessel shape after clamping was performed. The results were confirmed by in vivo experimentation with 60 rat aortas (of 1.8 to 2.4 mm caliber) using a variable-force clamp gauge developed in our laboratory. Experimental and theoretical results differed by only 3 gm. Scanning electron microscopy revealed that the initial changes in the endothelium occurred in smaller radii of curvature. Increased pressure resulted in gross morphological changes across the vessel. The minimum occlusion force (as determined by the variable-force clamp gauge) produced only minimal endothelial damage.     

Application of thrombolytic therapy in vascular occlusive disease. A surgical view

The use of fibrinolytic agents to control the fibrinolytic enzyme system and lyse pathologic fibrin deposits or thrombus has now assumed a position with anticoagulants and vascular surgery in the physician's therapeutic armamentarium. The principal exogenous activators that are used clinically are streptokinase, urokinase, and tissue plasminogen activator. Acute arterial occlusions are more likely than chronic occlusions to respond to thrombolytic therapy, especially if treatment is instituted within a few hours of onset of symptoms and if the disease is due to embolic material rather than in situ thrombosis. Since the duration of drug infusion necessary to lyse arterial thrombus cannot be predicted, patients in whom tissue viability cannot be determined or in whom ischemia cannot be tolerated during the drug infusion interval are not candidates for intraarterial fibrinolytic drug infusion. In treating patients with venous occlusion, thrombolytic therapy is more effective against proximal clots than in calf thrombosis. No protective effect from pulmonary embolism has been noted in trials comparing heparin with streptokinase. Fifty percent of patients with an initial episode of deep venous thrombosis treated within 72 hours of onset will have complete resolution of thrombus with preservation of valve function.     

Lipoprotein(a) in patients with proteinuria.

Lipoprotein(a) (Lp(a)) has recently been recognized to be a risk factor for coronary heart disease. Lp(a) median values in the absence of renal disease are around 10 mg/dl. Higher levels (greater than or equal to 30 mg/dl) correlate with the occurrence of coronary heart disease, particularly in the presence of elevated cholesterol. We have studied Lp(a) in 76 adults with proteinuria. Fifty had glomerular diseases and 26 non-glomerular diseases, with renal function varying from normal to advanced chronic renal failure. Lp(a) values were shifted to the right, with a median of 21.0 mg/dl, and 25% of patients had values of 30 mg/dl or more. Lp(a) did not correlate with cholesterol, age, lipoprotein subclasses, apoproteins A-I or B-100, albumin, creatinine, or creatinine clearance. Median Lp(a) values did not differ significantly comparing men versus women, or glomerular versus non-glomerular disease. Lp(a) may inhibit fibrinolysis, and is deposited in atherosclerotic lesions. Although the cause of these elevated Lp(a) levels is uncertain, we propose that they contribute to the increased risk of coronary heart disease in the nephrotic syndrome, and may play a role in progressive renal disease.     

Retroperitoneal inflow procedures for iliac occlusive vascular disease

We reviewed our experience over the past six years with retroperitoneal inflow procedures (aortofemoral and iliofemoral bypass grafts) in high-risk patients with aortoiliac occlusive disease. There were 57 limbs in 40 patients. Twenty percent of the patients were diabetic, 80% were smokers, 40% had heart disease, 54% had hypertension, and 25% had symptomatic chronic obstructive pulmonary disease. The average patient age was 64 years. There was no operative mortality and cumulative patency rate by life-table analysis at four years was 84%. The site of the proximal anastomosis (aorta vs iliac) or the configuration of the graft (unifemoral vs bifemoral) did not influence the patency rate. Retroperitoneal inflow procedures are an excellent alternative in patients who present an unacceptably high risk for standard aortofemoral reconstruction.     

Experience with fibrinolytic therapy of vascular occlusive disease

1. There may well be a place for streptokinase therapy in selected patients with chronic arterial occlusion, but the emphasis should be on developing information on selection criteria. 2. Efficacy and safety have been established for the use of streptokinase in occluded AV cannulae, but this may be more of historical than contemporary importance. 3. Although more investigation is required to define the role of lytic therapy in retinal vascular occlusion and in the hemolytic uremic syndrome, the preliminary results are encouraging and merit further attention.     

Laboratory evaluation of patients with vascular occlusive disease

In addition to the determination of the presenting symptom of patients with peripheral vascular occlusive disease, evaluation of these patients may include the noninvasive measurements of ankle/arm pressure ratio, limb blood flow, and treadmill testing to evaluate the severity of the reduction in blood flow. We have included metabolic studies to assess the effect of this reduced blood flow in patients with stable intermittent claudication (n = 20), and with end-stage ischemia (night and rest pain) (n = 11), and in a control group without vascular disease (n = 8). No correlations were found between the resting limb blood flow, ankle/arm pressure ratios, maximum walking distance, and stated walking distance for the patients with stable claudication. Although the oxygen consumption was reduced only in the patients with end-stage ischemia, the percent oxygen extraction was increased to the same level in the patients with stable claudication and those with end-stage ischemia. Intramuscular stores of high-energy phosphates and glycogen were maintained in all groups with the lactate/pyruvate ratio increased only in the patients with end-stage ischemia. The complex interrelationships between the rate and distribution of blood flow with exercise and enzyme adaptation in patients with vascular disease make current resting hemodynamic and metabolic evaluations a poor reflection of the severity of the clinical condition within each patient group. Therefore laboratory testing may offer no advantage over clinical presentation in the overall evaluation of these patients.