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Biomedical subjects

D H Blankenhorn

Publications and source records attributed to D H Blankenhorn.

At least 19 recordsLinked to original sources
PubMed1996

Progression of coronary artery disease predicts clinical coronary events. Long-term follow-up from the Cholesterol Lowering Atherosclerosis Study.

BACKGROUND: Progression of coronary artery disease is assumed to be a surrogate end point for clinical coronary events. Because no single method or measure for a coronary angiographic end point is uniformly accepted as optimal, the utility and validity of surrogate end points for predicting clinical coronary events remain unsettled. METHODS AND RESULTS: The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet. Atherosclerosis change on 2-year coronary angiograms was evaluated by a consensus panel and by quantitative coronary angiography (average per-subject change in percent diameter stenosis [%S] and minimum lumen diameter [MLD). With all three end points, the benefit of colestipol/niacin treatment on coronary artery atherosclerosis has been reported. Annual follow-up for an average of 7 years (range, 6.3 months to 10 years) has been carried out on all subjects who completed the 2-year angiogram. Clinical coronary events (need for revascularization, nonfatal acute myocardial infarction, and coronary death) have been documented. Risk of clinical coronary events was positively related to coronary lesion progression for all three surrogate end points (P<.05). New lesion formation in bypass grafts (P=.02) and progression of mild/moderate lesions ( < 50%S) were predictive of clinical coronary events (P<.01). Change in MLD contributed significantly to the prediction of clinical coronary events beyond a model with %S alone (P<.05). CONCLUSIONS: In this population of nonsmoking men with previous bypass surgery, both the consensus panel- and quantitative coronary angiography-based end points of coronary artery disease progression predict clinical coronary events. Subjects who demonstrate greater coronary artery lesion progression have an increased risk of future clinical coronary events. Design of shorter, smaller trials of antiatherosclerotic agents is justified.

Adult↗
PubMed1994

Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS).

To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal.

This review explores evidence for the reversibility of atherosclerosis and augmentation of angiography with non-invasive arterial wall imaging. Meta-analysis from coronary angiographic trials demonstrates that regression and stabilization are 1.5 to 2 times more common in treated than placebo subjects, and progression is reduced by half in treated subjects. Odds ratios for clinical coronary events are significantly reduced with treatment. Lesion improvement occurs more readily in women than men and more so in women receiving concomitant estrogen replacement therapy. Lesions with > or = 50% diameter stenosis (%S) at baseline respond more readily to lipid lowering than those < 50% S, whereas reduction in coronary events is related to stabilization of lesions < 50% S. Lipoproteins have a differential effect on lesion progression according to lesion size, and triglyceride-rich lipoproteins play an important role in the progression of coronary artery lesions < 50% S. Improved therapeutic regimens to alter progression of atherosclerosis may require adjunctive therapy, such as with antioxidants or hormone replacement therapy, in concert with low-density lipoprotein cholesterol reduction to prevent new lesion formation or early lesion progression. Sequential coronary angiographic determination of progression evaluated by both quantitative coronary angiography and global change score, a visual assessment of overall lesion change, predicts clinical coronary events. Only inferences about the state of the arterial wall can be made from angiography, because it delineates only the lumen. Therapy testing and study of atherosclerosis progression can be improved with noninvasive B-mode ultrasonographic imaging of the distal common carotid artery far-wall intima-media thickness (IMT), a reliable measure of early preintrusive atherosclerosis. Measurement of common carotid IMT is useful for the study of coronary artery risk factors and can augment studies of coronary artery intrusive lesions, because it is associated with coronary artery disease. B-mode measurement of common carotid IMT has the potential of serving as a noninvasive surrogate end point for clinical coronary events. Screening for peripheral vessel changes indicative of high risk for coronary artery disease is possible and cost-effective with the noninvasive procedures now available.

Arteriosclerosis↗
PubMed1994

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

BACKGROUND: The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets. METHODS AND RESULTS: Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor. CONCLUSIONS: These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.

Adult↗
PubMed1993

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

Adult↗
PubMed1993

Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound.

BACKGROUND: Controlled clinical trials have reported treatment effects evaluated with serial imaging in coronary and femoral but not cervical arteries. The Cholesterol Lowering Atherosclerosis Study, a coronary, cervical, and femoral angiographic trial of colestipol plus niacin, included a pilot study of standardized carotid ultrasound imaging. METHODS AND RESULTS: Seventy-eight subjects had ultrasound studies at baseline, 2, and 4 years. Twenty-four drug and 22 placebo subjects had carotid ultrasound images at baseline, 2, and 4 years with matching cervical angiograms. Computer image processing was applied to ultrasound images of common carotid (far wall) and cervical angiograms. Computer operators were blind to treatment group. Carotid ultrasound measurements were tested for treatment effects and compared with measurements of atherosclerosis in coronary and cervical angiograms. Drug subjects showed significant progressive reduction in carotid thickness at 2 (P = .0001) and 4 years (P = .0001); placebo subjects significantly increased wall thickness at 2 and 4 years. Reduced levels of apolipoprotein B and increased levels of high density lipoprotein cholesterol and apolipoprotein C-III were significant predictors of carotid wall thinning. Ultrasound-measured carotid intima-media thickness was correlated at baseline with visually read coronary angiographic stenosis and at 2 years with a robust computer measurement of mild carotid atherosclerosis. CONCLUSIONS: Common carotid intima-media thickening can be reduced by colestipol-niacin treatment. Two-year image-processed carotid ultrasound trials can provide adequate power with 50 subjects per group to test for this treatment effect.

Adult↗
PubMed1993

One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy.

BACKGROUND AND PURPOSE: The Cholesterol Lowering Atherosclerosis Study has reported significant reduction of coronary artery disease and of carotid arterial intima-media thickness (IMT) at 2 and 4 years with colestipol/niacin therapy. We now report on treatment effects on carotid IMT at 6 months and 1 year. METHODS: One hundred eighty-eight nonsmoking men, aged 40 to 59 years, with prior coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet therapy or placebo plus diet therapy. Computerized image processing of carotid ultrasound films was used to measure IMT in the right common carotid artery. Treatment group comparisons were made at 6 months and 1 year (46 and 33 subjects, respectively, with baseline and 6-month or 1-year ultrasound measures). The time course of the treatment effect on carotid IMT was estimated using the complete sample of 78 subjects with baseline and on-trial data. RESULTS: No significant treatment group differences on carotid IMT were found at 6 months. At 1 year, the treated group showed significant reduction of carotid IMT (P = .01 between groups). The placebo group showed continuing progression of IMT during the 4-year study period (estimated progression rate, 0.018 mm/y). The treated group showed reduction of IMT during the first 3 years and a plateau during the remainder of the study. CONCLUSIONS: Reduction of carotid IMT was found with aggressive lipid-lowering therapy. Ultrasound measures of IMT offer a noninvasive and precise measure of early carotid atherosclerosis that will decrease sample size requirements, potentially decrease dropout rates, and widen the study population of antiatherosclerotic clinical trials.

Adult↗
PubMed1993

Atherosclerosis--reversal with therapy.

Evidence for atherosclerosis reversal comes from studies in animals wherein atherosclerosis is induced and then allowed to regress, autopsy studies of starved humans, and angiographic studies testing antiatherosclerosis treatment. Animal models and autopsy studies have provided detailed histologic and biochemical descriptions of regression. Cellular and subcellular information exists on what can occur, but because the same lesions are not re-examined, what actually does occur is unknown. Studies of isolated arterial cell systems and intact lesions indicate that atherogenesis involves at least the following: Increased permeability of the endothelium to macromolecules such as low-density lipoprotein; platelet adherence to areas of functional endothelial injury or denudation; the entrance of monocytes or macrophages and lymphocytes into the subintimal space; and the secretion of growth factors by platelets, injured endothelium, and macrophages. These processes can be initiated or enhanced by various vasoactive agents that induce endothelial cell constriction with the opening of endothelial junctions. These processes also can recruit smooth muscle cells from the media to the subintima where they proliferate. Proliferating smooth muscle cells, along with macrophages, can internalize lipids and lipoproteins to form foam cells. Subintimal smooth muscle cells can also synthesize collagen, elastin, glycosaminoglycans, and other connective tissue elements that trap lipoproteins. Peroxidative injury increases the atherogenic potential of both cholesteryl ester-rich (low-density) and triglyceride-rich (very-low-density and intermediate-density) lipoproteins. Steep oxygen gradients within the arterial wall create local conditions for free radical generation, and any increase in residence time of lipoprotein particles can be atherogenic. In summary, there are many areas where treatment may retard or reverse atherogenesis. Angiographic trials that identify and track individual human lesions have shown that reducing known atherogenic risk factors can lessen coronary and femoral atherosclerosis. But they provide no information on events within arterial wall cells or the intracellular matrix. They deal only with lesions that intrude into the vessel lumen and obtain measurements at infrequent intervals. The weight of evidence is that regression is possible, but there is no consensus on the most effective therapy. The challenge for future trials is to select optimal targets for intervention among the known atherogenic processes.

Animals↗
PubMed1993

The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus.

Lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine were studied in 18 female patients with systemic lupus erythematosus (SLE) with mild or inactive disease. Patients were case matched (200-400 mg hydroxychloroquine daily vs no hydroxychloroquine) on several factors including daily corticosteroid dose in this cross sectional study. All had normal menstrual cycles; none smoked, used alcohol, were taking lipid altering medications or had other concurrent diseases. Patients taking hydroxychloroquine had 35-54% lower total triglyceride, VLDL-triglyceride, LDL-triglyceride, HDL-triglyceride, VLDL-cholesterol, and apolipoprotein CIII levels (p < 0.03). These results are encouraging in that hydroxychloroquine, in addition to being useful for alleviating the primary symptoms of SLE, may also be useful for ameliorating the adverse effects of corticosteroid therapy on triglyceride-rich lipoprotein metabolism.

Adult↗
PubMed1992

Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials.

The Cholesterol Lowering Atherosclerosis Study, a randomized angiographic clinical trial, demonstrated the beneficial effect of niacin/colestipol plus diet therapy on coronary atherosclerosis. Outcome was determined by panel-based estimates (viewed in both still and cine modes) of percent stenosis severity and change in native artery and bypass graft lesions. Computer-based quantitative coronary angiography (QCA) was also used to measure lesion and bypass graft stenosis severity and change in individual frames closely matched in orientation, opacification, and cardiac phase. Both methods jointly evaluated 350 nonoccluded lesions. The correlation between QCA and panel estimates of lesion size was 0.70 (p less than 0.0001) and for change in lesion size was 0.28 (p = 0.002). Agreement between the two methods in classifying lesion changes (i.e., regression, unchanged, or progression) occurred for 60% (210 of 350) of the lesions kappa +/- SEM = 0.20 +/- 0.05, p less than 0.001). The panel identified 442 nonoccluded lesions for which QCA stenosis measurements could not be obtained. Lesions not measurable by QCA included those with stenosis greater than 85% that could not be reliably edge tracked, segments with diffuse or ecstatic disease that had no reliable reference diameter, and segments for which matched frames could not be located. Seventy-nine lesions, the majority between 21% and 40% stenosis, were identified and measured by QCA but were not identified by the panel. This comparison study demonstrates the need to consider available angiographic measurement methods in relation to the goals of their use.

Adult↗
PubMed1992

Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect.

BACKGROUND: The Cholesterol Lowering Atherosclerosis Study has demonstrated beneficial effect of colestipol/niacin on coronary atherosclerosis using a panel-determined global coronary change score. We now report treatment group comparisons using quantitative coronary angiographic (QCA) measures from all processable segments in 85 of 162 randomly selected baseline/2-year film pairs. METHODS AND RESULTS: Treatment benefit was established for percent stenosis for either continuous or categorical analyses with regression established regardless of the per-patient scoring procedure. In addition, treatment benefit favoring regression was established in some cases for roughness and for percent involvement, a longitudinal estimate of the percent of coronary surface involved by raised lesions. Benefit on minimum diameter was directly related to whether the segment was proximal to a graft insertion and hemodynamically related to the bypass graft. QCA correlates of panel-determined progression were increases in percent stenosis and numbers of occluded lesions in native arteries and the number of progressing lesions in bypass grafts. CONCLUSIONS: These results demonstrate that a variety of computer measures can be used as end points in coronary angiographic therapy trials, but change in percent stenosis correlates best with visual panel assessments and best reflects the treatment benefit; when treatment effect sizes are moderate to large, the required sample size of coronary angiographic trials can be reduced when QCA is used.

Adult↗
PubMed1992

Regression of atherosclerosis: which components regress and what influences their reversal.

Two major features of atherosclerosis may be distinguished: (a) atherosis caused by lipid infiltration in cells and extracellularly and (b) sclerosis caused by connective tissue deposition and by functional disturbance of the endothelium, leading to impairment of endothelium-derived relaxing factor (EDRF)-release and reduced arterial compliance. Atherosis generally rarely causes clinical symptoms and, furthermore, is reversible by lowering of LDL-C. However, the clinically significant human lesion is the fibrous atheromatous plaque. Regression of established fibrous lesions by maximal lowering of LDL-C is slow in native coronary arteries and nonexistent in bypass grafts. However, there is good evidence from recent clinical trials that even in arteries with significant fibrous plaques, functional improvement of sclerosis (increased compliance) can be achieved by reducing maximally LDL-C in spite of remaining structural connective tissue abnormalities, presumably through normalization of EDRF. Atherosclerosis, therefore, appears to be best influenced by lipid lowering when it is in its atherosis phase. In the plaques of advanced atherosclerosis, when connective tissue sclerosis is present, agents working through mechanisms other than lipid lowering appear to be required for plaque reversal.

Animals↗
PubMed1991

Fat and cholesterol intake of attendees at two national USA cardiovascular annual meetings.

Using a 1-page bar-coded food frequency questionnaire, the food habits of 996 adults who participated in diet screening at the annual meetings of the American Heart Association (1989) and the American College of Cardiology (1990) were analyzed for sex, age and regional differences. Estimated nutrient intakes were also compared with those from the Department of Agriculture's 1985 and 1986 Continuing Survey of Food Intake of Individuals. The average diet reported in this study satisfied National Cholesterol Education Program guidelines for cholesterol intake, but was higher than that recommended for total and saturated fats. In addition, dietary fat intake was influenced by sex, age and geographic region. Reduction in total and saturated fat intake was confined to men greater than 35 years of age; intake of these nutrients was highest among young, Mid-western women. These results suggest the need for diet intervention programs, targeted specifically to young adults with additional consideration given to regional variation. Repeated surveys of cardiac care givers might be used as an early indicator of the nationwide effectiveness of dietary intervention programs.

Adult↗
PubMed1991

Regression of atherosclerosis: what does it mean?

Angiographic evidence of coronary artery atherosclerosis regression has been demonstrated in controlled clinical trials. The significance of this regression appears to depend in a complex way on the degree of atherosclerosis present when a regression regimen is initiated. Angiographic trials indicate that lesion change is a continuum, with a gradual transition from progression to stability and regression. Divergent lesion change can be seen in the same patient with a progression of some lesions and a regression of others. This makes it necessary to perform a comprehensive survey of all visible coronary segments when evaluating angiograms to determine the outcome of a clinical trial. An important finding in clinical trials is that new lesion formation can be reduced. This indicates that effective control of atherosclerosis may be possible with procedures now available, but noninvasive coronary artery imaging methods need to be refined.

Adult↗
PubMed1991

Relationship of arterial wall uptake of radiolabeled liposomes to the presence of monocyte/macrophage cells in the hypertensive and atherosclerotic arterial wall.

In vivo radiolabeled liposome uptake in 5 sham-operated, 7 coarctation-induced hypertensive, and 8 atherosclerotic arterial walls from New Zealand White rabbits was compared to determine the mechanism of arterial wall uptake of liposomes. Uptake between the three groups was significantly different (P less than 0.001) with a 3-fold difference in uptake between the sham-operated and hypertensive groups and the hypertensive and atherosclerotic groups. Liposome uptake was significantly higher in the atherosclerotic group of animals (P less than 0.05). Avidin-biotin immunoperoxidase staining for monocyte/macrophage cells revealed that liposome uptake increased concomitantly with arterial wall monocyte/macrophage cellular invasion and that liposome localization, determined by autoradiography, paralleled the monocyte/macrophage cellular distribution in both hypertensive and atherosclerotic arterial walls. This study provides the first direct evidence that liposomes can escape from the circulation and enter the diseased arterial wall. Furthermore, it suggests that one possible mechanism of arterial wall uptake of liposomes is via the monocyte/macrophage cell which avidly and preferentially engulfs liposomes and then passively carries them into the arterial wall during hypertensive and atherosclerotic lesion development. Liposomes could potentially be used to carry agents into the arterial wall in the study of arterial wall lesion development.

Animals↗
PubMed1991

Arterial wall oxygenation, oxyradicals, and atherosclerosis.

The oxygen supply of inner media and thickened intima of atherosclerosis prone arteries depends largely on diffusion from the endothelium. Conditions which increase wall thickness and oxygen diffusion or reduce oxygen transmissibility produce hypoxia and steep PO2 gradients within the wall. Cerebral injury and myocardial reperfusion studies indicate that intermittent hypoxia and steep PO2 gradients lead to oxyradical formation and tissue damage. Products of lipid and sterol peroxidation are found in atherosclerotic plaques and can be generated by arterial wall cells in culture. It is likely that peroxidation occurs directly within the arterial wall. Sufficient oxyradical generation occurs during normal oxygen metabolism that local scavenger mechanisms are required to avoid tissue damage. Experimental hypertension, hyperlipemia and balloon injury produce medial hypoxia with steep PO2 gradients and redistribution of the pattern of arterial wall antioxidant enzymes. This suggests that minor deviations from normal arterial wall anatomy and function can lead to oxyradicals which can be directly injurious and can amplify the atherogenic potential of lipoprotein infiltration.

Animals↗