Progression of coronary atherosclerosis. Clues to pathogenesis from serial coronary arteriography

Fifty two patients with coronary artery disease underwent repeat coronary arteriographic studies separated by 2-108 (mean 51) months of medical treatment. The results were compared and correlated with symptoms to determine the nature of the progression of coronary atherosclerosis. The condition appeared to progress episodically in the proximal segments of the coronary arteries and in relation to the abrupt development of new symptoms or acute coronary events such as unstable angina or myocardial infarction. Thirty four of 105 (33%) of the pre-existing stenoses showed evidence of progression. Progression to total occlusion was uncommon (13) except for stenoses greater than 90% (six out of 18). New lesions frequently occurred (37) in previously normal segments of the arteries; most of these were stenoses greater than 90% (13) or total occlusions (12). Rapid progression of a mild lesion and new lesions occurred in the form of smooth intimal protrusions into the arterial lumen. Intimal haemorrhages are the likely explanation for these intimal encroachments and also for the episodic nature of the progression of coronary artery disease. Coronary atherosclerosis does not progress gradually in a linear fashion, and local anatomical factors appear to play a dominant role in the natural history.     

Progression of coronary atherosclerosis from adolescents to mature adults

Ten selected topographic sites of the coronary arteries were placed in sequence according to age, sex, branching anatomical pattern and smoking habit, in order to obtain an indirect sequencing of the pattern and rate of progression of early atherosclerotic lesions from adolescents to mature adults. The material came from 356 subjects aged 16-45 years who had died in violent accidents and included the light-microscopic examination of 3560 coronary artery samples. The dynamic reconstruction of thousands of static views revealed the existence of an age-related rate of progression of fibromuscular plaques, intimal necrotic areas, incorporated microthrombi and fatty streaks. All these early atherosclerotic lesions increased linearly and in parallel from one 5-year age group to the next and exhibited non-significant differences in their rate of progression over a period of 25 years. During this period the number of atherosclerotic plaques increased 4.7 times, of intimal necrotic areas 4.6 times, of incorporated microthrombi 4.3 times and of fatty streaks 3.9 times. Consequently, in the 10 selected topographic sites of the coronary arteries placed in sequence according to age, the pathological aspects became prevalent, microscopically, over the normal ones, starting from the fourth decade of life. This study also revealed that some endogenous and exogenous risk factors for coronary heart disease accelerated the age-related rate of progression of early atherosclerotic lesions. In addition, particular cycles of evolution towards advanced lesions appeared, leading to the onset of fibronecrotic and fibrohyaline plaques. Their obstructive character was related to both successive incorporation of microthrombi and the onset of large lipid deposits. Among the four types of early atherosclerotic lesions investigated, only the fatty streaks did not show this direct conversion to a lesion of possible clinical significance.     

Clues to DVT pathogenesis

In this issue of Blood, Brill and colleagues demonstrate that von Willebrand factor (VWF) release and subsequent platelet adhesion to endothelial cells are required for thrombus formation in a mouse model of deep venous thrombosis (DVT).     

Follow-up study of coronary artery lesions due to Kawasaki disease by serial selective coronary arteriography in 200 patients

Summary In a follow-up study of coronary artery lesions (CAL) due to Kawasaki disease, 200 patients were examined by serial coronary arteriography 1 year after first detection of the condition. On comparing the findings of the two coronary angiographic studies, a worsening of stenotic lesions was detected in 30 patients (15%; 40 of 139 stenotic lesions, 29%), while improvement of stenotic lesions was seen in 24 patients (12%; 40 lesions, 29%). Relating these changes in CAL to the interval from the onset of disease to the first coronary arteriography showed the rate of increased or new stenotic lesions (37%) to be higher in the late group, in which the first study was performed 5 months after the onset of the disease, than in the early group (21%), in which the study was done within 4 months from the disease onset. The frequency of decrease in aneurysm size was higher in the early group (70%) than in the late group (19%).Supported by grant no. 9 from the Japan Heart Foundation     

A morphometric study of the distribution of early coronary atherosclerosis using arteriography

In order to document the localized prevalence of early atherosclerosis in the major coronary arteries, a study using 50 coronary arteriographies was made from Feb. 1984 to Sep. 1985 in Shinshu University Hospital. Early atherosclerotic stenosis had a spatial distribution with strong incidence on the LAD bifurcations which contained the first diagonal branch, RCA which contained RV branches and LCX which contained the OM branch. Upstream of the bifurcations, the stenotic changes were observed to be concentric with the vessel axes. Downstream of the flowdivider, the lesions were gathered proximally and quickly disappeared distally. Lesions tended to occur eccentrically at the lateral walls of the entrance of the smaller branch. The proximal portions of both the RCA and LCA were almost free of disease. We also tried to investigate the relationship between the bifurcation angle branching off the parent vessels and early sclerotic lesions. We found that the angle between the branches and the plane in contact with the surface of the heart is especially important.     

Post-heparin lipases, lipids and related hormones in men undergoing coronary arteriography to assess atherosclerosis

Post-heparin lipase activities were measured in normolipemic men with complaints suggestive of symptomatic coronary artery disease. A study group, who showed diffuse atherosclerotic narrowing of the coronary vessels, assessed by a quantitative computer-assisted analysis method, had a lowered hepatic lipase in comparison with a group with normal angiograms. Lipoprotein lipase was lower in the study group but well within the normal range and not statistically different. Some related hormones (cortisol, estradiol, testosterone and glucagon) were different in the two groups while others (insulin, human growth hormone, prolactin, thyroid hormones) were not. The results are discussed in view of the proposed role of hepatic lipase in the uptake of HDL-cholesterol by the liver.     

Effect of lipid-lowering therapy on the progression of coronary atherosclerosis assessed by scheduled repetitive coronary arteriography

We studied 42 subjects, each of whom demonstrated significant (?50%) narrowing of a non-grafted coronary artery and a baseline cholesterol level >250 mg%. All patients underwent repeat scheduled coronary arteriography after 2 years on the study. Twenty-five colestipol responders (cholesterol levels reduced at least 15% within 1 month of therapy) were compared to 17 non-responders who were given 23 months of placebo after a 1 month exposure to colestipol. Baseline risk factors and demographic characteristics were similar for the two groups. In comparison to baseline arteriography, only 3 of the 25 drug-treated patients showed progression, while 8 of 17 placebo treated patients demonstrated progression (P = 0.011). Drug-treated patients demonstrated a 20% decrease in cholesterol levels, while placebo patients did not experience a significant reduction in cholesterol levels.Our study suggests that significant reduction in serum cholesterol levels is associated with a reduced likelihood of progression of coronary atherosclerotic lesions assessed by scheduled repetitive coronary arteriography in hyperlipidemic subjects demonstrating significant coronary artery narrowing on their initial arteriograms.     

Some clinical considerations regarding the relation of coronary vasospasm to coronary atherosclerosis: A hypothetical pathogenesis

This study explores the relation between coronary arterial spasm and the development of coronary atherosclerosis. The clinical history and coronary angiographic and electrocardiographic data in 212 consecutive patients with ischemic heart disease were correlated. These patients were classified into four groups: Group 1, patients without angiographic evidence of atherosclerosis; Group 2, patients with single vessel disease; Group 3, patients with double vessel disease; and Group 4, patients with significant narrowing of major coronary arteries. Although spontaneous angina occurred in all four groups, it was more common (55 percent) in the patients in Group 1, who were predominantly female and young. Spontaneous angina was confirmed in Group 1 with several techniques, including thallium-201 scintigraphy, ergonovine administration and electrocardiography during attacks of pain. Prior myocardial infarction was present with similar frequency in all four groups. A patient is discussed whose spontaneously occurring coronary arterial spasm later progressed to fixed arteriosclerotic narrowing requiring coronary bypass surgery. These observations and a review of the literature lend support to the hypothesis that coronary arterial spasm can be a possible antecedent leading to the later development of fixed atherosclerotic coronary arterial obstruction.     

Progression of carotid atherosclerosis in Japanese patients with coronary artery disease

The authors investigated the relationship between the progression of carotid atherosclerosis and the severity of coronary artery disease (CAD). The two-year follow-ups of extracranial carotid atherosclerosis in 50 patients with CAD were evaluated by B-mode high-resolution ultrasonography. The summed maximal thickness of carotid plaques increased by 3.2 to 10.1 mm (mean 1.06 mm, SD 2.42 mm). The extent of coronary atherosclerosis (p<0.02) and the serum total cholesterol level (p<0.01) were different between the progressing group (n=20) and the nonprogressing group (n=25) with carotid atherosclerosis. Carotid disease progression was significantly higher in patients with three-vessel coronary disease than in those without significant coronary disease (p<0.005). Age, serum triglyceride, high-density lipoprotein-cholesterol, pack-years of smoking, % smokers, % hypertensives, and % diabetics were not different between the two groups. It was concluded that the severity of CAD was one of the strong predictors for carotid disease progression in patients with CAD.     

Progression of coronary atherosclerosis and the non-invasive evaluation in older patients

To evaluate characteristics of coronary atherosclerosis in older patients and to elucidate the role of dipyridamole myocardial perfusion scintigraphy (DMPS) in the assessment of patients with coronary artery disease, 437 patients (330 men, 107 women, age range 13-85 years) initially underwent coronary angiography (CAG) and DMPS. Coronary risk factors were evaluated in relation to the severity and progression of coronary atherosclerosis. Cardiac events were also evaluated during the follow-up period of 39 +/- 19 months (range 1-77 months). Assessment of five coronary risk factors, including hypercholesterolemia, diabetes, hypertension, positive family history, and history of smoking, was made in 212 patients in relation to the severity of coronary atherosclerosis. In patients with insignificant lesions or single vessel disease, prevalence of hypercholesterolemia and positive family history was lower in older patients (65 years or older) than in younger patients (64 years or younger), but significant difference was not found in prevalence of diabetes, hypertension, and history of smoking. In patients with multivessel disease, there was no significant difference in prevalence of coronary risk factors between the two groups except history of smoking. Repeated CAG was performed in 27 patients during follow-up. Nineteen of them experienced increased symptoms of angina and eight patients newly developed acute myocardial infarction. The patients with increased angina had more risk factors, and majority of them (74%) showed some progression of previously noted severe stenoses in the proximal coronary arteries. In patients with new infarction, 62% of them showed new total occlusions as infarct-related lesions, although there were some patients who showed progression of previously noted severe lesions. DMPS was performed in 437 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toll样受体4与冠状动脉粥样硬化关系的研究进展

Toll样受体(Toll like receptors,TLRs)是与果蝇Toll蛋白具有同源性的表达于细胞膜上与免疫系统识别微生物有关的一类受体家族,能够识别特定类型微生物的保守分子成分,即病原体相关分子模式(pathogen-associated molecular patterns,PAMPs),如TLR4识别脂多糖(lipopolysaccha-ri     

Progression of coronary atherosclerosis quantified by analysis of 3-D reconstruction of left coronary arteries

Objectives: Quantitative measurements on three-dimensional (3-D) reconstructed coronary trees permit accurate evaluation of vascular volumes, lengths and diameters. We applied this technique to investigate diffuse luminal narrowing in patients with the clinical manifestation of progressive atherosclerosis. Methods: In 13 patients who presented repeatedly for coronary angioplasty (at least 4 years of invasive follow-up), left coronary arteries were reconstructed in 3-D from biplane coronary angiograms. Mean diameter, cross-sectional areas, total length, and volume were calculated for segments and branches. Five patients without coronary artery disease served as controls. Results: Patients with progressive coronary atherosclerosis demonstrated a significant reduction of total vascular volumes, mean diameters and cross-sectional areas at the initial investigation when compared with controls. Progressive luminal shrinkage occurred during follow-up (−0.04±0.13 mm per year and per segmental diameter). The progress of luminal narrowing in patients with coronary artery disease is related to the number of coronary risk factors and the duration of follow-up. Conclusion: Quantitative measurements on 3-D reconstructed coronary trees are a useful investigative tool for the assessment of progression of coronary atherosclerosis.