Effects of cardiovascular risk factors on coronary artery remodeling in patients with mild atherosclerosis

BACKGROUND: Vascular remodeling counteracts luminal encroachment during the progression of coronary artery disease (CAD) and modulates the manifestation of hemodynamically significant lesions. However, the role of cardiovascular risk factors for coronary remodeling has not been fully clarified. METHODS: Therefore, we investigated the role of local plaque burden and systemic risk factors on coronary vascular remodeling in 25 patients (49 segments) with angiographically normal or minimally diseased coronary arteries by intravascular ultrasound. In an additional 12 patients without coronary atherosclerosis, physiological vessel tapering was determined and used to calculate the extent of remodeling in diseased segments. RESULTS: An increase in local plaque burden was directly correlated with positive vascular remodeling (r = 0.54, P<0.001). However, cardiovascular risk factors like hypertension (P<0.001) and hypercholesterolemia (P = 0.03) were associated with reduced positive or even negative remodeling. Moreover, the total number of classical cardiovascular risk factors was a strong predictor for reduced positive remodeling (P for trend <0.001). In contrast, coronary flow reserve, a measure of shear stress imposed on the vessel wall, positively correlated with compensatory enlargement (r = 0.44, P = 0.002). By multivariate analysis, plaque burden (P = 0.001), hypertension (P = 0.001) and coronary flow reserve (P = 0.018) proved to be independent determinants of vascular remodeling of epicardial coronary arteries. CONCLUSIONS: Cardiovascular risk factors impair compensatory arterial enlargement and even predispose to shrinkage of epicardial arteries during the initial stage of atherosclerosis. Reduced positive vascular remodeling might contribute to the clinical manifestation of CAD by facilitating the development of flow-limiting stenoses in patients at risk.     

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.     

High-density lipoprotein cholesterol in coronary artery disease patients: is it as low as expected?

OBJECTIVE: Epidemiological studies demonstrated that the high-density lipoprotein (HDL) cholesterol levels in Turkish people are lower compared to other populations. In the present study, the HDL cholesterol levels in subjects with or without angiographically documented coronary artery disease (CAD) were compared to assess whether HDL cholesterol levels were as low as expected. METHODS: A total of 420 consecutive patients with age of > or =40 years (160 female, 260 male) undergoing coronary angiography were included in the study. Patients receiving fibric acid derivatives or niacin were excluded. Coronary artery disease group consisted of those patients with any atherosclerotic lesions in coronary angiography, and non-CAD group consisted of patients with no such lesions. RESULTS: Average HDL cholesterol levels were 45.0+/-10.5 mg/dl (44.4+/-10.9 mg/dl in men, 46.5+/-9.6 mg/dl in women) in CAD group, and 47.7+/-9.0 mg/dl (45.5+/-8.4 mg/dl in men, 48.9+/-9.2 mg/dl in women) in non-CAD group (p<0.05). CONCLUSION: Compared to non-CAD patients, patients with CAD had lower HDL cholesterol levels, but in general HDL cholesterol levels were not as low as to be expected from epidemiological studies.     

Intravascular ultrasonic analysis of plaque characteristics associated with coronary artery remodeling.

We sought to determine the patient and plaque characteristics associated with the different forms of arterial remodeling as seen by intravascular ultrasound (IVUS) before coronary intervention. Remodeling in response to plaque accumulation may occur in the form of compensatory enlargement and/or focal vessel contraction. Previous studies report variation in the frequency and form of arterial remodeling. We performed preintervention IVUS imaging on 169 patients. Vessels were categorized as exhibiting compensatory enlargement or focal contraction if the arterial area at the lesion was larger or smaller, respectively, than both proximal and distal reference arterial areas; otherwise the artery was considered not to have undergone significant remodeling. Calcification was assessed and noncalcified plaque density was measured by videodensitometry. Sixty-one of 169 patients (66 narrowings) (46 men and 15 women, age 56+/-11 years) had adequate reference segments. Remodeling occurred in 43 of 66 patients (65%): compensatory enlargement in 27 of 66 (41%) and focal contraction in 16 of 66 (24%). Lesions with focal contraction had significantly smaller arterial area (13.3+/-3.3 vs. 18.1+/-7.0 mm2, p = 0.02) and plaque area (9.5+/-2.8 vs 13.7+/-5.5 mm2, p<0.01). Cross-sectional stenosis was similar (71+/-9% vs. 75+/-10%, p = NS), as was plaque density (p = 0.20), eccentricity, and calcium. Patient age, gender, and lesion location were not related to the form of remodeling. Similarly, history of diabetes, hypercholesterolemia, or hypertension was not predictive. Smoking was the only risk factor associated with focal contraction (p<0.01). Thus, whereas compensatory enlargement appears to be the most common form of coronary artery remodeling, focal contraction occurs more often in smokers.     

Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity.

Recent evidence suggests that high-density lipoprotein (HDL) cholesterol has important vasoactive properties which may contribute to its beneficial effects on atherosclerotic coronary artery disease. The endothelium-dependent vasodilator acetylcholine has been used in a number of experimental studies to assess endothelial function. The relation between serum lipoproteins and acetylcholine-induced coronary vasoreactivity was investigated in patients (n = 27) undergoing elective coronary arteriography. Mean serum cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglyceride levels were 189 +/- 7 (4.84 +/- 0.18 mmol/liter), 134 +/- 6 (3.47 +/- 0.15 mmol/liter), 41 +/- 3 (1.06 +/- 0.08 mmol/liter) and 106 +/- 30 mg/dl (1.20 +/- 0.03 mmol/liter), respectively. After a baseline arteriogram, acetylcholine was infused into the left main coronary artery and percent change from baseline dimension was determined in 27 angiographically smooth coronary artery segments and in 14 arterial segments with evidence of mild atherosclerotic disease. Intact vascular smooth muscle function was then confirmed in all segments by dilation to intracoronary nitroglycerin. Acetylcholine produced significant vasoconstriction of both angiographically smooth (13 +/- 4%, p less than 0.05 vs baseline) and diseased (19 +/- 4%, p less than 0.05 vs baseline) coronary segments. A positive correlation was observed between HDL cholesterol and normal acetylcholine-induced coronary vasoreactivity in both angiographically smooth (r = 0.59, p less than 0.001) and diseased (r = 0.62, p less than 0.02) coronary segments. No significant correlation was observed, however, between total and low-density lipoprotein cholesterol, or between total cholesterol to HDL ratio and the response of coronary artery diameter to acetylcholine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of lipid-lowering therapy on coronary artery remodeling

BACKGROUND: Although lipid-lowering therapy affects the luminal size of atherosclerotic coronary arteries the role of vascular remodeling has not been systematically studied. DESIGN/METHODS: Serial three-dimensional volumetric intravascular ultrasound (IVUS) was used to study remodeling, which was defined as changes in arterial size independent of or dependent on changes in plaque size. Using an automated contour detection algorithm, a 1 mm segment of a moderate atherosclerotic lesion at the site of the maximal plaque volume at baseline was analysed. After 12 months the relationship between the absolute change in vessel volume and plaque volume was calculated in 99 patients. There was a significant relationship between changes in plaque and vessel volume, independent of plaque progression or plaque regression (decrease in plaque size, r = 0.60, P < 0.0001 and increase in plaque size, r = 0.49, P < 0.0008, respectively; the slopes of the regression equation were 1.03 and 0.80). By means of an analysis of covariance we tested whether the regression slopes were equal between groups of patients as defined by the low-density lipoprotein-cholesterol (LDL-c) level achieved with lipid-lowering therapy. RESULTS: Only patients with plaque progression and a LDL-c level < 100 mg/dl had a significantly smaller slope than patients with a LDL-c level > 100 mg/dl (-0.14 compared with 1.14, P = 0.003 ), indicating diminished coronary remodeling. CONCLUSIONS: Serial volumetric IVUS confirms the existence of both positive and negative remodeling in relation to an increase and decrease in plaque volume. It has been shown that the outward remodeling process is diminished in patients with plaque progression and intensive lipid-lowering therapy.     

The influence of plaque orientation (pericardial or myocardial) on coronary arterial remodeling

BACKGROUND: Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined. METHODS: Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA(lesion)/VA(reference)) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95-1.05, negative<0.95) as well as remodeling index (RI, VA(lesion)-VA(reference)/PA(lesion)-PA(reference)). RESULTS: The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78+/-0.72, M 10.26+/-0.50 mm(2), P<0.05) and VA (P 15.71+/-0.90, M 12.82+/-0.57 mm(2), P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03+/-0.03, M 0.86+/-0.03, P<0.01) and RI (P 0.02+/-0.07, M -1.10+/-0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01). CONCLUSIONS: Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.     

Relation between baseline plaque burden and subsequent remodelling of atherosclerotic left main coronary arteries: a serial intravascular ultrasound study with long-term (> or =12 months) follow-up.

AIMS: Glagov's histopathological observation and non-serial intravascular ultrasound studies (IVUS) concluded that compensatory coronary remodelling diminishes as 40% atherosclerotic plaque burden is reached. We tested this hypothesis with serial IVUS. METHODS AND RESULTS: Serial IVUS examinations of 46 atherosclerotic non-stenotic left main stems (18+/-8 months apart) were analysed to assess the relation between baseline plaque burden (=plaque+media area/vessel area) vs. serial remodelling (=vessel area at baseline - at follow-up). There were 25 plaques with baseline plaque burden <40% (30.1+/-6.6%, group A) and 21 plaques with baseline plaque burden > or =40% (46.1+/-5.8%, group B). There was no relation between baseline plaque burden vs. subsequent changes in vessel area overall (r=0.07, P=0.7), for group A (r=0.03, P=0.6), and group B (r=0.01, P=0.8). The frequency of positive serial remodelling (vessel area increase) vs. negative or intermediate serial remodelling (no change or decrease) were similar in group A [17 (68%) vs. 8 (32%)] and group B lesions [18 (86%) vs. 3 (14%)] (P=0.2). CONCLUSION: IVUS demonstrates that serial coronary remodelling is not related to baseline plaque burden. Lesions with baseline plaque burden <40% may subsequently show a lack of compensation or frank arterial shrinkage, whereas lesions with baseline plaque burden >40% may continue to develop compensatory enlargement.     

Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients

Familial hypercholesterolemia (FH) is characterized by an autosomal codominant inheritance, an abnormality in low-density lipoprotein (LDL) receptor function, elevated plasma cholesterol levels and premature atherosclerosis. Sixteen patients with homozygous FH were studied to correlate the extent of their atherosclerotic disease with their lipid levels and receptor function. The age range at initial presentation was 3 to 38 years (mean 12), and at the last examination, 6 to 43 years (mean 20). The mean pretreatment total plasma cholesterol concentration for all patients was 729 +/- 58 mg/dl (+/- standard error of the mean), and the mean LDL cholesterol level was 672 +/- 58 mg/dl (normal 60 to 176). High-density lipoprotein cholesterol was 28 +/- 3 mg/dl (normal 30 to 74). In the 7 patients with FH who had symptoms of myocardial ischemia (Group I), the mean pretreatment LDL cholesterol value (817 +/- 62 mg/dl) was higher than that of the 9 asymptomatic patients (Group II) (560 +/- 74 mg/dl). In Group I, 5 of 7 patients had left or right coronary ostial narrowing and 3 had significant left ventricular outflow obstruction. Most coronary arterial narrowing occurred in the right coronary and left anterior descending arteries and the least amount in the left circumflex coronary artery. A femoral bruit was the physical finding that correlated best with the Group I population; brother:sister pairs revealed a milder clinical course for the female. Seven of the 16 patients have survived into their third decade without symptoms. Comparison of these persons with those in whom angina developed reveals a marked heterogeneity in their clinical course, which appears to be associated with receptor negative/defective status.     

Effect of Hypertension on Coronary Remodeling Patterns in Angiographically Normal or Minimally Atherosclerotic Coronary Arteries: An Intravascular Ultrasound Study

Whether there is any particular role of hypertension in remodeling process has not been completely understood yet. The aim of this study was to assess the association between hypertension and remodeling patterns in normal or minimally atherosclerotic coronary arteries. Seventy-nine patients who were free of significant coronary atherosclerosis were divided into two groups according to the absence (n = 39) or presence (n = 40) of hypertension; and standard intravascular ultrasound examination was performed in 145 segments. To determine the remodeling pattern in early atherosclerotic process, patients were also analyzed according to the level of plaque burden at the lesion site after the analysis of remodeling patterns. Positive remodeling was more prevalent in the hypertensive group (52.5% vs. 12.8%; P < .001) whereas negative remodeling was more common in diabetic patients (53.6% vs. 27.4%; P = .03). Mean remodeling index was 1.04 for hypertensives and 0.96 for normotensives (P = .03). There were no correlations between remodeling patterns and other risk factors such as age, family history, and hypercholesterolemia. Early atherosclerotic lesions (<30%) exhibited more negative remodeling characteristics while intermediate pattern was observed more frequently in patients with high plaque burden (P = .006 and .02, respectively). Positive remodeling showed no association in this context (P = .07). This study demonstrated that minimal atherosclerotic lesions in hypertensives had a tendency for compensatory arterial enlargement. Positive remodeling may result from local adaptive processes within vessel wall or hemodynamic effects of blood pressure itself.     

Cholesterol-lowering treatment is associated with improvement in coronary vascular remodeling and endothelial function in patients with normal or mildly diseased coronary arteries

Coronary vascular remodeling and altered endothelial function have been described in the early stages of native atherosclerosis. The purpose of this study was to evaluate the association between cholesterol-lowering therapy and coronary vascular remodeling and endothelial function in patients with normal or mildly diseases coronary arteries. Patients (N=101) with normal or mildly diseased coronary arteries by coronary angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Vessel and lumen area, atherosclerotic plaque area, and plaque morphology were evaluated. Vascular reactivity was examined with the use of intracoronary adenosine, acetylcholine, and nitroglycerin. Patients were divided into 3 groups based on the total cholesterol levels: group 1 (n=25), patients with a history of hypercholesterolemia adequately treated (total cholesterol <240 mg/dL); group 2 (n=26), patients with hypercholesterolemia not adequately controlled (total cholesterol >/=240 mg/dL); and group 3 (n=50), patients without hypercholesterolemia. Vessel area and lumen area were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: vessel area 11.9+/-0.5, 10.6+/-0.4, and 11.8+/-0.4 mm(2), both P<0.05; lumen area 8.3+/-0.4, 6.9+/-0.3, and 8.9+/-0.3 mm(2), both P<0.01). However, plaque areas in groups 1 and 2 were similar. Furthermore, acetylcholine-induced percent increases in coronary blood flow were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: 70.5+/-20.1%, 22.8+/-13.7%, and 68.6+/-14.8%, both P<0. 05). Cholesterol-lowering treatment is associated with an improvement in coronary lumen area that results not from a decrease in plaque area but from an increase in vessel area, reflecting vascular remodeling. Additionally, this adaptive process may occur in association with an improvement of endothelium-dependent vasodilation of the resistance coronary artery.     

What has intravascular ultrasound taught us about plaque biology?

Intravascular ultrasound (IVUS) has a defined role in the cardiac catheterization laboratory to assess lesion severity and the procedural success of vascular interventions. However, IVUS has also contributed to our understanding of the biology of atherosclerosis and restenosis. In acute coronary syndromes, IVUS has revealed varying degrees of stenosis, thrombosis, and plaque derangement typical of the plaque disruption seen in many pathologic studies of patients who have died of this condition. IVUS has demonstrated that the culprit lesions of patients surviving acute coronary syndromes also tend to be softer, with less calcium, and tend to have more plaque with positive arterial remodeling (compensatory enlargement) than lesions causing stable coronary syndromes. Arterial remodeling is also an important component of restenosis after coronary interventions. IVUS has suggested that interventions that reduce restenosis tend to have a greater impact on preventing negative remodeling (constriction) rather than reducing neointimal proliferation. Oxidant stress may be an important contributor to negative remodeling, as IVUS has demonstrated this anatomy at sites of coronary artery spasm. Positive remodeling seen by IVUS is also associated with impaired endothelial vasomotor dysfunction, and IVUS studies have demonstrated the contribution of vasomotor tone to arterial elasticity. Future directions include integrating IVUS with other imaging modalities, such as angiography, to study the interaction of anatomic and physiologic factors in atherosclerosis progression, and using the raw ultrasound signal to distinguish plaque components and differences in wall strain that may identify vulnerable plaques.     

Effect of atherosclerotic regression on total luminal size of coronary arteries as determined by intravascular ultrasound

We assessed vascular changes during atherosclerosis regression. Compensatory enlargement of coronary arteries accommodates plaque burden during atherosclerosis development. Lipid-lowering therapy has altered the natural history of coronary atherosclerosis, but the arterial changes that occur during disease regression need to be clarified. Intravascular ultrasound was performed at baseline and after approximately 18 months in 432 patients with coronary disease. Mean plaque, lumen, and total vessel area were computed in a 30-mm coronary segment of interest. Mean low-density lipoprotein cholesterol level was 2.4 mmol/L, and 88% of patients received statins. Overall, changes in plaque and total vessel areas were highly correlated (r = 0.82, p <0.0001). Among the 227 patients with plaque regression, the plaque area decrease was -0.58 +/- 0.54 mm(2), and changes in total vessel and lumen areas were -1.02 +/- 1.10 and -0.44 +/- 0.86 mm(2), respectively. The decrease in plaque area correlated better with the change in total vessel area (r = 0.64, p <0.0001) than with the change in lumen area (r = 0.20, p = 0.003). The relation between plaque regression and decrease in total vessel area was significantly better (p = 0.019) for patients with a >40% atheroma area (r = 0.72; p <0.0001) than for those with 相似文献   

血管内超声分析斑块组成与冠状动脉重构之间的关系

目的 本研究的目的旨在应用血管内超声显像(IVUS)技术探讨斑块组成与冠状动脉重构之间的关系.方法 对77例冠心病患者(男性53例,平均年龄58±10岁)的罪犯血管采用ClearView或Galaxy2 (美国波士顿科学公司)血管内超声显像仪进行IVUS检查,其中31例为稳定性心绞痛,46例为急性冠状动脉综合征.对病变进行定性和定量测定.根据斑块组成回声的不同,分为软斑块、纤维斑块、钙化斑块和混合斑块,后三者统称为硬斑块.重构指数(RI)=病变处血管横截面积/平均参考血管面积.若RI＞1.0为正性重构;RI＜1.0为负性重构.比较不同重构形式病变的特性.结果 77处病变中,45处(58%)发生正性重构,32处(42%)发生负性重构.比较两组患者的临床表现,正性重构的患者更多的表现为急性冠状动脉综合征(74%比43%, P=0.006).与负性重构相比,正性重构病变部位的斑块面积和血管面积较大,斑块组成更多为软斑块(71%比34%, P＝0.001),发生钙化的较少(21%比54%, P＝0.003),钙化范围也较小[(18±37)°比(40±50)°, P＝0.027].进行多因素回归分析后,斑块组成和临床表现在两组患者中的差别仍具有统计学意义.结论冠状动脉重构与临床表现及斑块组成有关,正性重构病变软斑块较多见且钙化较少.     

Effect of coronary risk factors on arterial compensatory enlargement in japanese middle-aged patients with de novo single-vessel disease--an intravascular ultrasound study

BACKGROUND: Compensatory enlargement (CE) of atherosclerotic human arteries has been reported; however, the pattern of arterial remodeling in response to plaque formation is not unique. HYPOTHESIS: The study was undertaken to determine the extent of coronary artery compensatory enlargement at stenotic lesions and to correlate the arterial compensatory enlargement with risk factors. METHODS: We studied 62 patients with stable angina and de novo single-vessel disease using intravascular ultrasound and obtained good images in 42 patients (68%). The vessel cross-sectional area (VA), lumen cross-sectional area (LA), and plaque cross-sectional area (PA) were measured at the lesion site and at proximal and distal reference sites. Positive CE was defined as increase in VA of lesion site > 10% compared with that of proximal reference site (CE group, n = 15); shrinkage was defined as reduction in VA of lesion site > 10% compared with that of proximal reference site (S group, n = 14); inadequate CE was defined as intermediate between CE and S (IE group, n = 13). All subjects had coronary risk factors measured before this study. RESULTS: There was no difference in VA, LA, or PA among the three groups at the proximal and distal reference sites, nor in LA at the lesion site; however, VA and PA were significantly smaller in the S group than in the other groups (p < 0.01). Of coronary risk factors, increased systolic blood pressure (SBP), increased diastolic blood pressure (DBP), and decreased high-density lipoprotein cholesterol (HDL-c) levels had the strongest association with shrinkage (p < 0.05). CONCLUSION: Hypertension and decreased HDL level may contribute to the shrinkage response in middle-aged patients with stable angina.     

Compensatory enlargement and stenosis develop in apoE(-/-) and apoE*3-Leiden transgenic mice

Atherosclerotic mouse models develop little ischemic organ damage and no infarctions, despite the presence of large atherosclerotic lesions. Therefore, we hypothesize that luminal changes do not follow atherosclerotic lesion development. Because a phenomenon that may explain the discrepancy between luminal changes and lesion size is vascular remodeling, we measured parameters of vascular remodeling in the carotid arteries (CAs), thoracic aorta (TA), and abdominal aorta (AA) of apolipoprotein E (apoE)-deficient (apoE(-/-)) and apoE*3-Leiden mice, 2 well-known mouse models of atherosclerosis. Atherosclerotic lesions were classified (American Heart Association [AHA] types II through V), and plaque thickness, compensatory enlargement versus constrictive remodeling, lumen diameter, stenosis, and media thickness were measured relative to the nondiseased arterial wall. In CAs, plaque thickness increased during atherogenesis. CAs showed compensatory enlargement (apoE(-/-) 55%, apoE*3-Leiden 38%). Regression analysis revealed a positive correlation between plaque and lumen area (for apoE(-/-), R=0.95; for apoE*3-Leiden, R=0.90). Medial thinning and elastolysis were also observed. During atherogenesis, lumen diameter decreased (apoE(-/-) -69%, apoE*3-Leiden -40%), and stenosis >70% developed. TA and AA showed similar features, but neither developed a progressive decrease in lumen diameter or stenosis >70%. In CAs, TA, and AA of apoE(-/-) and apoE*3-Leiden mice, atherogenesis is associated with compensatory enlargement, medial thinning, and elastolysis. A progressive decrease in lumen diameter and stenoses >70% occur only in CAs. Vascular remodeling is more prominent in apoE(-/-) mice.     

Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3) in non-insulin-dependent diabetics with coronary artery disease

STATEMENT OF THE PROBLEM: Low levels of high-density lipoprotein cholesterol (HDL-C) have a strong association with coronary artery disease (CAD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). In this study, we tried to evaluate whether one or both of the major HDL subclasses (HDL2, HDL3) is strongly associated with the risk of CAD in NIDDM subjects. METHODS: The separation of HDL subclasses was carried out by ultracentrifugation in a Beckman Airfuge. HDL2 subclass was isolated from the supernatant and its cholesterol content was measured enzymatically. Plasma HDL3 cholesterol was calculated as the difference between results for total HDL cholesterol and HDL2 cholesterol. RESULTS: NIDDM patients with CAD had significantly higher triglyceride levels compared to either control (217.09+/-55.04 versus 89.62+/-31.29 mg/dl, P=.001) or CAD patients without NIDDM (217.09+/-55.04 versus 156.28+/-46.39 mg/dl, P<.05). However, in the diabetic patients with CAD, there was a statistically significant decrease in HDL cholesterol (39.63+/-8.59 versus 55.86+/-13.49 mg/dl, P<.01), HDL2 cholesterol (8.74+/-3.28 versus 16.95+/-5.73 mg/dl, P<.001), and HDL3 cholesterol (31.23+/-7.41 versus 38.91+/-8.93 mg/dl, P<.05) in comparison to nondiabetic controls. Moreover, in the comparison between non-insulin-dependent diabetics with CAD and CAD subjects without NIDDM, HDL cholesterol (39.63+/-8.59 versus 46.13+/-6.33 mg/dl, P<.05) and HDL2 cholesterol (8.74+/-3.28 versus 11.84+/-4.01 mg/dl, P<.02) were significantly reduced, while HDL3 cholesterol levels were (31.23+/-7.41 versus 34.29+/-7.94 mg/dl, P=.92) unaltered. Additionally, the percentage reduction of cholesterol in HDL2 fraction was proportionately greater than the decrease in HDL3 subclass in both comparisons. Moreover, in NIDDM with CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol by 48% and 26%, and HDL3 cholesterol by 20% and 9%, compared relatively to controls and CAD subjects without NIDDM. CONCLUSIONS: In conclusion, HDL2 is the more variable subclass and reflects changes in HDL. This suggests that the protective role of total HDL against CAD is mainly mediated through HDL2 fraction. Therefore, HDL2 might be a better predictor of coronary heart disease than total HDL, in non-insulin-dependent diabetes mellitus.     

Intravascular ultrasound evaluation of coronary plaque regression by low density lipoprotein-apheresis in familial hypercholesterolemia: the Low Density Lipoprotein-Apheresis Coronary Morphology and Reserve Trial (LACMART)

OBJECTIVES: We sought to assess the effects of low density lipoprotein (LDL)-apheresis (LDL-A) for regression of coronary plaque in familial hypercholesterolemia (FH), we set up a one-year follow-up multicenter trial using coronary angiography and intravascular ultrasound (IVUS). BACKGROUND: It is still unclear whether aggressive lipid-lowering therapy by LDL-A leads to the regression of coronary plaque in patients with FH. METHODS: Eighteen patients with FH were assigned to one of two groups: medication + LDL-A (LDL-A group, n = 11) and medication only (medication group, n = 7). Total cholesterol, triglycerides, high density lipoprotein cholesterol and LDL cholesterol were measured in all subjects at the outset of treatment (baseline) and every three months thereafter. Coronary angiography and IVUS were performed at the outset and after the one-year follow-up period to measure minimal lumen diameter (MLD) by coronary angiogram and plaque area (PA) by IVUS. RESULTS: The LDL-A group showed 28.4% reduction in total cholesterol (from 275 +/- 27 mg/dl to 197 +/- 19 mg/dl) and 34.3% reduction in LDL cholesterol (from 213 +/- 25 mg/dl to 140 +/- 27 mg/dl) after one-year follow-up, while the medication group showed no changes in cholesterol levels. There were significant interactions between both treatments in total cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), MLD (p = 0.008) and PA (p = 0.017) using two-way repeated-measures analysis of variance by the SAS system (SAS Institute Inc., Cary, North Carolina). Significant differences were seen in net change in MLD (p = 0.004) and PA (p = 0.008) during the one-year follow-up period between both groups. CONCLUSIONS: These results suggest that aggressive lipid-lowering therapy using the combination of LDL-A and lipid-lowering drugs may induce regression of coronary atherosclerotic plaque in FH patients.     

Koronares Risikoprofil bei Frauen mit angiographisch normalen Koronararterien oder initialer Koronararteriosklerose

The pathophysiology and prognosis of coronary heart disease in women are the subject of intensive epidemiological and clinical investigations due to sex specific considerations. We have estimated the prevalence of modifiable coronary risk factors in 36 consecutive women (mean age 59.7 years) with suspected coronary heart disease in whom coronary angiography was performed due to unclear chest pain. Seventeen women revealed angiographically normal coronary arteries (gr. I) and 19 women showed coronary vessels with initial arteriosclerosis (luminal diameter reduction < 35%) (gr. II). Mean age was 59.1 years in gr. I and 60.3 years in gr. II (p = ns). No woman received lipid lowering drugs within the last 6 months. A hormone replacement therapy was not performed in any case. Women in gr. I showed significantly higher total and LDL cholesterol levels (271.6 +/- 34.3 vs 243.5 +/- 44.8 mg/dl; p < 0.005 and 190.5 +/- 36.8 vs 149.7 +/- 45.1 mg/dl; p < 0.025, respectively) and significantly lower HDL cholesterol values (57.8 +/- 16.5 vs 72.8 +/- 19.1 mg/dl; p < 0.0125) compared to women in gr. II. The total/HDL cholesterol ratio was 3.6 +/- 1.2 in gr. I and 5.1 +/- 1.7 in gr. II (p < 0.005). The positive predictive value for the existence of initial coronary atherosclerosis and a total cholesterol/HDL ratio > 4 was 76.5%. The negative predictive value and a ratio < 4 was 81.3%. Women in gr. I revealed 1.2 +/- 0.9 and in gr. II 1.6 +/- 0.8 risk factors (smoking, hypertension, body mass index > 30 kg/m2, diabetes mellitus, hyperlipidemia) (p < 0.10). The 10-year risk for the occurrence of a coronary event was 9.1 +/- 3.7% in gr. I and 14.2 +/- 5.8% in gr. II (p < 0.005). The positive predictive value for the existence of initial coronary atherosclerosis and a 10-year risk > 10% was 90%. The negative predictive value and a 10-year risk < 10% was 64.0%. Our investigation indicates that women with a mean age of 60 years, unclear chest pain and without exercise induced ischemia are highly suspected to have initial coronary arteriosclerosis, when a distinct risk factor profile and a 10-year cardiac event risk > 10% are present. For this high risk group of women, intensive secondary prevention measures are necessary.     

Intravascular ultrasound findings of negative arterial remodeling at sites of focal coronary spasm in patients with vasospastic angina

BACKGROUND: There are few data about the intravascular ultrasound (IVUS) findings in patients with vasospastic angina, especially regarding patterns of vascular remodeling. METHODS AND RESULTS: Coronary spasm was documented by angiography and electrocardiographic evidence of ischemia in 36 patients after administration of ergonovine (cumulative doses up to 350 microg). After relief of spasm with 1000 microg of intracoronary nitroglycerin, quantitative angiography and IVUS imaging were performed and analyzed by standard methods. The 36 focal spasm sites were compared with the proximal and distal reference segments. The angiographic baseline minimum lumen diameter measured 1.78 +/- 0.66 mm, which decreased to 0.66 +/- 0.38 mm with ergonovine provocation (P <.0001), increased to 2.66 +/- 0.64 mm after intracoronary nitroglycerin (P <.0001 compared with baseline and after ergonovine), and did not change after IVUS imaging (2.66 +/- 0.63, P =.9). By IVUS, atherosclerotic lesions were observed at all coronary spasm sites; the mean plaque burden measured 56% at the spasm site and 35% at the reference. Spasm site plaque composition was hypoechoic in 31 and hyperechoic, noncalcific in 5; there was no calcium. The mean eccentricity index (maximum divided by minimum plaque thickness) was 6.7. Positive remodeling (spasm site arterial area greater than proximal reference) was present in 5; intermediate remodeling (proximal reference greater than spasm site greater than distal reference arterial area) was present in 7; and negative remodeling (spasm site arterial area less than distal reference) was present in 24. CONCLUSIONS: Sites of vasospasm in patients with variant angina showed characteristics of early atherosclerosis, except for an unusually high incidence of negative arterial remodeling.