N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine.

CONTEXT: Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. OBJECTIVE: Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. MATERIALS AND METHODS: Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 µg.kg⁻¹), 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml⁻¹ Mucomyst™ at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. RESULTS: Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO2) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO2) significantly increased, and arterial blood pH and bicarbonate (HCO3⁻) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO3⁻ levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. DISCUSSION: NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving clinically relevant physiological indices affected by sulfur mustard exposure. CONCLUSION: Beneficial effects of nebulized NAC were apparent following inhaled sulfur mustard exposure. Further therapeutic benefit may result from a combination therapy approach.

Effect of transforming growth factor-beta and growth differentiation factor-5 on proliferation and matrix production by human bone marrow stromal cells cultured on braided poly lactic-co-glycolic acid scaffolds for ligament tissue engineering.

Tissue engineering of ligaments based on biomechanically suitable biomaterials combined with autologous cells may provide a solution for the drawbacks associated with conventional graft material. The aim of the present study was to investigate the contribution of recombinant human transforming growth factor beta 1 (rhTGF-beta1) and growth differentiation factor (GDF)-5, known for their role in connective tissue regeneration, to proliferation and matrix production by human bone marrow stromal cells (BMSCs) cultured onto woven, bioabsorbable, 3-dimensional (3D) poly(lactic-co-glycolic acid) scaffolds. Cells were cultured for 12 days in the presence or absence of these growth factors at different concentrations. Human BMSCs attached to the suture material, proliferated, and synthesized extracellular matrix rich in collagen type I and collagen III. No differentiation was demonstrated toward cartilage or bone tissue. The addition of rhTGF-beta1 (1-10 ng/mL) and GDF-5 (10-100 ng/mL) increased cell content (p < 0.05), but only TGF-beta1 also increased total collagen production (p < 0.05) and collagen production per cell, which is a parameter indicating differentiation. In conclusion, stimulation with rhTGF-beta1, and to a lesser extent with GDF-5, can modulate human BMSCs toward collagenous soft tissue when applied to a 3D hybrid construct. The use of growth factors could play an important role in the improvement of ligament tissue engineering.

Mid-term results of arthroscopic reconstruction in chronic posterior cruciate ligament instability.

The purpose of this study was to evaluate the clinical results of arthroscopic single bundle posterior cruciate ligament (PCL) reconstruction in patients with chronic PCL instability not responding to conservative treatment. 18 patients were available for follow-up with an average elapsed time of 3 years between onset of injury and surgery and an average duration of 3.3 years between reconstruction and evaluation. The clinical results were investigated using the IKDC form, the Tegner rating system, a subjective evaluation, and the VAS for pain rating. The presence of femoral degenerative changes correlated strongly to the elapsed time between injury and operation (P<0.05). Before surgery all patients were graded D (severely abnormal) using the IKDC evaluation form. The final IKDC score at follow-up resulted in grade A (normal) in five patients (28%), grade B (nearly normal) in eight patients (44%), grade C (abnormal) in four patients (22%) and grade D (severely abnormal) in one patient (6%). The VAS score for pain rating revealed very few complaints of pain and it demonstrated a strong correlation between the subjective evaluation and the Tegner rating score (P<0.01). Evaluation of the Tegner score resulted in a significant improvement after surgery when compared to the situation prior to operation (P<0.01). Although there still is some controversy on the indication for treatment of PCL injury, we conclude on the basis of our findings that arthroscopic reconstruction of symptomatic chronic PCL instability, not responding to conservative therapy, can be greatly beneficial.

Glycosylation and lectins-examples of immunesurveillance and immune evasion.

Cell surface proteins are posttranslationally modified by tightly regulated enzymes of glycosylation. Typical patterns of glycosylation may signal pathological situations to the immune system. Here, carbohydrate receptors on the surface of cells in the immune system are involved in regulation of effector cells. Moreover, some lectins are circulating in the plasma and take part in host defense. The code of carbohydrate modifications is impaired in malignant cells and yet they are not eliminated. In this review, we focus on recent experimental evidence for regulatory functions of lectins and carbohydrate derivatives in the immune system and tumours.

Lipoprotein (a) and the risk of ischemic stroke in young women.

BACKGROUND AND PURPOSE: lipoprotein (a) (lp (a)) is a lipid-containing particle similar to LDL which has been found in atherosclerotic plaque. The role of lp (a) in ischemic stroke remains controversial, but some studies suggest lp (a) is particularly important as a risk factor for stroke in young adults. We investigated the role of lp (a) as a risk factor for stroke in young women enrolled in the Stroke Prevention in Young Women Study. METHODS: subjects were participants in a population-based, case-control study of risk factors for ischemic stroke in young women. Cases were derived from surveillance of 59 regional hospitals in the central Maryland, Washington DC, Pennsylvania and Delaware area. Lp (a) was measured in 110 cases and 216 age-matched controls. Demographics, risk factors, and stroke subtype were determined by interview and review of medical records. RESULTS: lp (a) values were higher in blacks than whites, but within racial groups, the distribution of lp (a) values was similar between cases and controls. After adjustment for age, race, hypertension, diabetes, cigarette smoking, coronary artery disease, total cholesterol and HDL cholesterol, the odds ratio for an association of lp (a) and stroke was 1.36 (95% CI 0.80-2.29). There was no dose-response relationship between lp (a) quintile and stroke risk. Among stroke subtypes, only lacunar stroke patients had significantly elevated lp (a) values compared to controls. CONCLUSIONS: we found no association of lp (a) with stroke in a population of young women with ischemic stroke. Small numbers of patients limit conclusions regarding risk in ischemic stroke subtypes, but we could not confirm previous suggestions of an association of lp (a) with atherosclerotic stroke in young adults.

Lipoprotein(a)-cholesterol and coronary heart disease in the Framingham Heart Study.

BACKGROUND: Increased plasma lipoprotein(a) [Lp(a)] concentrations have been reported to be an independent risk factor for coronary heart disease (CHD) in some prospective studies, but not in others. These inconsistencies may relate to a lack of standardization and the failure of some immunoassays to measure all apolipoprotein(a) isoforms equally. METHODS: We measured plasma Lp(a)-cholesterol [Lp(a)-C] in a Caucasian population of offspring and spouses of the Framingham Heart Study participants, using a lectin-based assay (LipoproTM). We compared the prevalence of increased Lp(a)-C to the presence of sinking pre-beta-lipoprotein (SPB). We also related Lp(a)-C concentrations to the prevalence of CHD risk in the entire population. RESULTS: The mean (+/- SD) Lp(a)-C concentration in the Framingham population (n = 3121) was 0.186 +/- 0.160 mmol/L, with no significant gender or age differences. The mean Lp(a)-C concentrations in the absence or presence of SPB were 0.158 +/- 0. 132 mmol/L and 0.453 +/- 0.220 mmol/L, respectively (P <0.0001). The mean Lp(a)-C concentration in men with CHD (n = 156) was 0.241 +/- 0. 204 mmol/L, which was significantly (P <0.001) higher, by 34%, than in controls. The odds ratio for CHD risk in men with Lp(a)-C >/=0. 259 mmol/L (>/=10 mg/dL), after adjusting for age, HDL-cholesterol, LDL-cholesterol, smoking, diabetes, blood pressure, and body mass index, was 2.293 (confidence interval, 1.55-3.94; P <0.0005). Lp(a)-C values correlated highly with a Lp(a)-mass immunoassay [ApotekTM Lp(a); r = 0.832; P <0.0001; n = 1000]. CONCLUSIONS: An increased Lp(a)-C value >/=0.259 mmol/L (>/=10 mg/dL) is an independent CHD risk factor in men with a relative risk of more than 2, but was inconclusive in women. Lp(a)-C measurements offer an alternative to Lp(a)-mass immunoassays and can be performed on automated analyzers.

Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study.

OBJECTIVE: To establish whether elevated lipoprotein(a) [Lp(a)], detected as a sinking pre-beta-lipoprotein band on electrophoresis of fresh plasma, is an independent risk factor for the development of premature coronary heart disease (CHD) in men. DESIGN AND SETTING: Prospective study of the Framingham offspring cohort. PARTICIPANTS: A total of 2191 men aged 20 to 54 years old who were free of cardiovascular disease when they were examined between 1971 and 1975. MAIN OUTCOME MEASURES: Incident CHD (myocardial infarction, coronary insufficiency, angina pectoris, or sudden cardiac death) occurring by age 55 years. RESULTS: After a median follow-up of 15.4 years, there were 129 CHD events. The relative risk (RR) estimates (with 95% confidence intervals [CIs]) for premature CHD derived from a proportional hazards model that included age, body mass index, and the dichotomized risk factor covariables elevated plasma Lp(a) level, total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, high-density lipoprotein (HDL) level less than 0.9 mmol/L (35 mg/dL), smoking, glucose intolerance, and hypertension were as follows: elevated Lp(a) level, RR, 1.9 (95% CI, 1.2-2.9), prevalence, 11.3%; total cholesterol level of 6.2 mmol/L or more, RR, 1.8 (95% CI, 1.2-2.7), prevalence, 14.3%; HDL level of less than 0.9 mmol/L, RR, 1.8 (95% CI, 1.2-2.6), prevalence 19.2%; smoking, RR 3.6 (95% CI, 2.2-5.5), prevalence, 46.7%; glucose intolerance, RR, 2.7 (95% CI, 1.4-5.3), prevalence, 2.6%; hypertension, RR, 1.2 (95% CI, 0.8-1.8), prevalence, 26.3%. CONCLUSIONS: Elevated plasma Lp(a) is an independent risk factor for the development of premature CHD in men, comparable in magnitude and prevalence (ie, attributable risk) to a total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, or an HDL level less than 0.9 mmol/L (35 mg/dL).

Demonstration of popliteal artery entrapment on leg muscle scintigraphy with 99mTc MIBI and single photon emission tomography.

Popliteal artery entrapment is difficult to diagnose even at surgery. Early diagnosis is important as the prognosis is better if detected before the onset of complications. There is no sensitive method for the evaluation of this condition. We describe three cases detected by a new technique using 99mTc methoxy isobutyl isonitrile (MIBI) with single photon emission tomography. The scintigraphic features of entrapment and the advantage of MIBI leg scintigraphy over other methods are discussed.

A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.

BACKGROUND: Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women. METHODS AND RESULTS: From 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band present versus absent groups were as follows: myocardial infarction (82 events), 2.37 (1.48 to 3.81); intermittent claudication (62 events), 1.94 (1.07 to 3.50); cerebrovascular disease (83 events), 1.88 (1.12 to 3.15); total coronary heart disease (174 events), 1.61 (1.13 to 2.29); and total cardiovascular disease (305 events), 1.44 (1.09 to 1.91). A subset analysis indicated that band presence was 50.9% sensitive and 95.4% specific for detecting plasma lipoprotein (a) levels of > 30 mg/dL, the threshold value linked to increased cardiovascular disease risk in men. CONCLUSIONS: Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein (a) levels in Framingham Heart Study women. Band presence and, equivalently, elevated plasma lipoprotein (a), was a strong, independent predictor of myocardial infarction, intermittent claudication, and cerebrovascular disease. Confirmation of these findings in other longitudinal studies of women is needed.

Coordination of aimed movements in a case of unilateral cerebellar damage.

We have studied multi-joint arm movements in a patient with right cerebellar damage. Our patient's kinetic tremor was reduced in the absence of visual feedback, but increased when performing a concurrent cognitive task. We suggest that her kinetic tremor reflects use of a slow cortical feedback circuit for error-corrections during movement. Analysing the spatial relation between hand aperture and hand transport in prehensile movements, we found preserved strategic, trial-to-trial coordination, but impaired reactive, within-trial coordination. We conclude that the proprioceptive representations provided by the normal cerebellum play an important role in coordinating multi-joint movement.

Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial.

OBJECTIVE: To examine the relationship between elevated levels of lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) risk in a prospective study. DESIGN: Nested case-control study. The cohort consisted of participants in the Lipid Research Clinics Coronary Primary Prevention Trial. SETTING: Lipid research clinics. PARTICIPANTS: The Lipid Research Clinics Coronary Primary Prevention Trial participants (n = 3806) were men, aged 35 to 59 years, with plasma cholesterol levels of 6.85 mmol/L (265 mg/dL) or greater, low-density lipoprotein cholesterol levels of 4.91 mmol/L (190 mg/dL) or greater, and triglyceride levels less than 3.39 mmol/L. Subjects were randomly assigned to either cholestyramine or placebo treatment. The Lp(a) levels were measured in plasma samples obtained prior to randomization in 233 cases (participants who developed CHD in the course of the study) and 390 matched CHD-free controls. A total of 96.95% of the subjects were white, 2.25% were black, and 0.80% were of other race. MAIN OUTCOME MEASURE: Coronary heart disease (either fatal or nonfatal) events during a follow-up of 7 to 10 years. RESULTS: The Lp(a) levels were significantly higher (21%) in cases than in controls (23.7 mg/dL [0.59 mmol/L] and 19.5 mg/dL [0.49 mmol/L], respectively; P < .02). This difference was still statistically significant (P < .01) after controlling for age, body mass index, cigarette smoking, blood pressure, low-density lipoprotein cholesterol level, and high-density lipoprotein cholesterol level. When subjects were divided by treatment, both cholestyramine-treated and placebo-treated CHD subjects had Lp(a) levels 20% to 22% greater than their matched controls. However, possibly because of smaller sample sizes, these differences were no longer statistically significant. CONCLUSIONS: Our data are consistent with the concept that an elevated Lp(a) level is an independent risk factor for CHD in hypercholesterolemic white men.

Rice bran oil consumption and plasma lipid levels in moderately hypercholesterolemic humans.

The effect of rice bran oil, and oil not commonly consumed in the United States, on plasma lipid and apolipoprotein concentrations was studied within the context of a National Cholesterol Education Panel (NCEP) Step 2 diet and compared with the effects of canola, corn, and olive oils. The study subjects were 15 middle-aged and elderly subjects (8 postmenopausal women and 7 men; age range, 44 to 78 years) with elevated low-density lipoprotein (LDL) cholesterol (C) concentrations (range, 133 to 219 mg/dL). Diets enriched in each of the test oils were consumed by each subject for 32-day periods in a double-blind fashion and were ordered in a Latin square design. All food and drink were provided by the metabolic research unit. Diet components were identical (17% of calories as protein, 53% as carbohydrate, 30% as fat [< 7% as saturated fat], and 80 mg cholesterol/1000 kcal) except that two thirds of the fat in each diet was contributed by rice bran, canola, corn, or olive oil. Mean +/- SD plasma total cholesterol concentrations were 192 +/- 19, 194 +/- 20, 194 +/- 19, and 205 +/- 19 mg/dL, and LDL-C concentrations were 109 +/- 30, 109 +/- 26, 108 +/- 31, and 112 +/- 29 mg/dL after consumption of the rice bran, canola, corn, and olive oil-enriched diets, respectively. Plasma cholesterol and LDL-C concentrations were similar and statistically indistinguishable when the subjects consumed the rice bran, canola, and corn oil-enriched diets and lower than when they consumed the olive oil-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program Step 2 diet.

The most stringent dietary recommendations of the National Cholesterol Education Program (NCEP) are to limit fat intake to < 30% of calories, saturated fat intake to < 7% of calories, and cholesterol intake to < 200 mg/d (Step 2 diet). There is debate as to whether the remaining fat in the diet should be relatively high in monounsaturated or polyunsaturated fatty acids. We examined this issue by testing the effects of diets meeting the aforementioned guidelines that were enriched in three different vegetable oils on plasma lipids in the fasting and postprandial states in a clinically relevant population. Female and male subjects (n = 15, mean age, 61 years) with low-density lipoprotein cholesterol (LDL-C) concentrations > 130 mg/dL were studied under strictly controlled conditions. Subjects were first placed on a diet similar to that currently consumed in the United States to stabilize plasma lipids with respect to identical fat and cholesterol intakes. The subjects then received diets meeting NCEP Step 2 criteria in which two thirds of the fat calories were given either as canola, corn, or olive oil in a randomized, double-blinded fashion for 32 days each. Plasma cholesterol concentrations declined after consumption of diets enriched in all the test oils; however, the declines were significantly greater for the canola (12%) and corn (13%) than for the olive (7%) oil-enriched diet. Mean plasma LDL-C concentrations declined after consumption of diets enriched in all the test oils (16%, 17%, and 13% for canola, corn, and olive oil, respectively), and the magnitude of the declines was statistically indistinguishable among the test oils. Mean plasma high-density lipoprotein cholesterol (HDL-C) concentrations declined after consumption of the baseline diet, and these declines were significant for the canola (7%) and corn (9%) oil-enriched diets. Changes in LDL apolipoprotein (apo)B concentrations paralleled those of LDL-C. Switching from the baseline to the vegetable oil--enriched diets had no significant effect on plasma triglyceride, apoA-I, and lipoprotein(a) concentrations or the total cholesterol to HDL-C ratio. LDL apoB to apoA-I ratios were significantly reduced when the subjects consumed the vegetable oil--enriched diets. Differences similar to those observed in the fasting state were observed in the postprandial state.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein. METHODS AND RESULTS: We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10-mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women. CONCLUSIONS: We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p < 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels.

Hydrogenation impairs the hypolipidemic effect of corn oil in humans. Hydrogenation, trans fatty acids, and plasma lipids.

The effects of plasma lipoproteins and apolipoproteins of replacing corn oil with corn-oil margarine in stick form as two thirds of the fat in the National Cholesterol Education Program (NCEP) Step 2 diet were assessed in 14 middle-aged and elderly women and men (age range, 44-78 years) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-C] range, 133-219 mg/dl [3.45-5.67 mmol/l] at screening). During each 32-day study phase, subjects received all their food and drink from a metabolic kitchen. Subjects were first studied while being fed a diet approximating the composition of the current US diet (baseline), which contained 35% of calories as fat (13% saturated fatty acids [SFAs], 12% monounsaturated fatty acids [MUFAs; 0.8% 18:1n-9 trans], and 8% polyunsaturated fatty acids [PUFAs]) and 128 mg cholesterol/1,000 kcal. This baseline phase was followed by a corn oil-enriched diet containing 30% fat (6% SFA, 11% MUFA [0.4% 18:1n-9 trans], and 10% PUFA) and 83 mg cholesterol/1,000 kcal, and then a corn-oil margarine-enriched diet containing 30% fat (8% SFA, 12% MUFA [4.2% 18:1n-9 trans], and 8% PUFA) and 77 mg cholesterol/1,000 kcal. All diets were isocaloric. Mean fasting LDL-C and apolipoprotein (apo) B levels were 153 mg/dl (3.96 mmol/l) and 101 mg/dl on the baseline diet, 17% and 20% lower (both p < 0.001) on the corn oil-enriched diet, and 10% and 10% lower (both p < 0.01) on the margarine-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Change in LDL particle size is associated with change in plasma triglyceride concentration.

Low density lipoprotein (LDL) particle size is inversely associated with plasma triglyceride concentration in cross-sectional analyses. In the present study, changes in the LDL particle size of 227 participants of the Framingham Offspring Study were analyzed longitudinally by nondenaturing gradient gel electrophoresis at two examinations that were separated by 3-4 years. All subjects had triglyceride concentrations < 400 mg/dl at both exams. Using laser scanning densitometry to assess mean LDL particle size, 56% of samples displayed a change in size: 41% had a one-band size change, 13% had a two-band change, and 2% had a three-band change. These changes in size corresponded to a 15% change in pattern type, based on pattern A and B terminology. There was a significant inverse association between change in LDL size and change in triglyceride (p < 0.0001) and glucose (p < 0.004) concentrations, body weight (p < 0.02), and age (p < 0.03). There was also a significant positive association with change in high density lipoprotein (HDL) cholesterol concentration (p < 0.0001). Change in LDL cholesterol concentration, as calculated by use of the Friedewald formula, however, showed no significant association with change in LDL size (p < 0.9). There was also no significant association with change in smoking or blood pressure, but there was a nonsignificant inverse trend associated with alcohol intake (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.

Prevalence of lipoprotein (a) [Lp(a)] excess in coronary artery disease.

Lipoprotein (a) [Lp(a)] is composed of 1 low-density lipoprotein (LDL) particle, to which 1 molecule of apolipoprotein (a) is covalently linked. Elevated levels of Lp(a) have been associated with coronary artery disease (CAD) and Lp(a) has been shown to be highly heritable. Our purpose was to determine the prevalence of familial Lp(a) excess in patients with CAD. We determined plasma levels of Lp(a) in 180 patients (150 men and 30 women) with angiographically documented CAD before age 60 years, and in 459 control subjects (276 men and 183 women) clinically free of cardiovascular disease. In addition, Lp(a) levels were determined in families of 102 of the CAD probands (87 men and 15 women). No gender differences in Lp(a) levels were observed between men and women (patients or control subjects). Patients with CAD had higher Lp(a) levels than did control subjects (19 +/- 21 vs 13 +/- 15 mg/dl, p less than 0.001). The prevalence of Lp(a) excess (defined as greater than 90th percentile of controls) was 17% in patients with CAD (p less than 0.05). Lp(a) levels were not correlated with cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol or apolipoproteins A-I or B. There was a weak correlation between Lp(a) and triglycerides (r = 0.166, p less than 0.05) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was a risk factor for the presence of CAD in men, independent of smoking, hypertension, diabetes, LDL and HDL cholesterol, or apolipoprotein A-I and B levels. Family studies revealed that Lp(a) levels are strongly genetically determined.(ABSTRACT TRUNCATED AT 250 WORDS)