Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ARTERIOSCLEROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Medium chain triglycerides (MCT) in aging and arteriosclerosis.

Some of the nutritional work with triglycerides consisting mainly of C8 and C10 fatty acids (MCT) lends itself to speculations about their influence on arteriosclerosis. Arteriosclerosis is thought to be part of the normal aging process which is due to age associated molecular biological changes. The lipid theory of arteriosclerosis is rejected. Pertinent studies with MCT include these observations. Feeding of MCT to rats resulted in animals of low body weight, small fat deposits and excellent survival rate. This deserves emphasis because of the beneficial influence of low body weight on aging and arteriosclerosis. MCT feeding was associated with low linoleate and low tocopherol requirements in rats. This may lead to reduced formation of those linoleate derived prostaglandins which favor thrombosis formation. Lower linoleate requirements may also lead to the presence of fewer uncontrolled free radicals in the cells. MCT feeding is associated with low levels of serum and liver cholesterol involving speculations that tissue conditions are such that an adaptive increase of cholesterol is unnecessary. The Demographic Yearbook of the United Nations (1978) reported that Sri Lanka has the lowest death rate from ischemic heart disease. Sri Lanka is the only of the countries giving reliable data where coconut oil (containing over 50% medium chain fatty acids) is the main dietary fat.

Aging↗
PubMed1986

[Role of trace elements in the dynamics of arteriosclerosis].

According to the present state of knowledge 7 quantitative elements and possibly 18 trace elements are of vital importance for the animal. Their metabolism is antagonistically or synergistically influenced by the inorganic and organic constituents of the food of different kind. More than 30 elements (Cu, Zn, Mg, Mn, Cr, V and so on) shall be connected with the process of arteriosclerosis. Cu-deficiency as well as Cu-abundance may increase the cholesterol content of the blood serum. Under conditions of Cu-deficiency the formation of the crosslinks of the elastin of the blood vessels is disturbed. Under conditions of Zn-deficiency the serum cholesterol content is as a rule, but not exceptionally decreased in the animal. Similarly unclear is the influence of high administrations of Zn on the process of arteriosclerosis. An Mg-deficit may lead to a whole chain of changes (disturbances of the cardiac rhythm, necrotic changes, atheromatous plaques, high values of total cholesterol, low values of HDL-cholesterol). Via the glucose tolerance factor a Cr-deficit possibly takes influence on the arteriosclerotic process. Hardness of the water, Mn, Pb, Ni, Mn shall also become effective. The Cu-Zn-relation as factor evoking arteriosclerosis further needs analysis. The investigations concerning arteriosclerosis in the animal experiment should in future be performed by means of semisynthetic rations, in order to render the results of the experiments comparable and to be able to control the large number of evoking factors.

Animals↗
PubMed1986

[Introduction to current problems in arteriosclerosis research].

Preliminarily is referred to essential aspects of the aetiology of arteriosclerosis with particular consideration of the disturbed lipoprotein metabolism. Morphologically in the centre of pathogenetic considerations is the behaviour of the endothelial cells, the smooth muscle cells and the blood macrophages. As in many cases open problems we refer to the different participation of various arterial parts of the vessels in the arteriosclerotic process, to the necessity of a further clarification of the role of the thrombocytes in the initial phase of the arteriosclerosis as well as to the monocytes and their possible importance for the elimination of lipids from the vascular wall, the influence of drugs on the proliferation of smooth muscle cells and the formation of extracellular matrix, the question of the regression of arteriosclerotic changes, the reduction of risk factors and their influence on the regression of morphological changes in various developmental stages of arteriosclerosis. It is referred to the possible importance of macrophages and their metabolism as markers for the recognition of risk-endangered persons. Furthermore is emphasized the importance of models for the clarification of the pathomechanism of the arteriosclerosis as well as of the cell culture and of perfusion models.

Arteriosclerosis↗
PubMed1979

[New aspects in the pathologic anatomy of arteriosclerosis obliterans].

The pathogenetic notion of arteriosclerosis and the clinical syndrome of the arterial obstructive diseases are not identical, but interfere in different points which are discussed in detail. Arteriosclerotic changes must be delimitated from pure age-conditioned changes of the arteries, since the two are sufficiently defined and deviate from each other in important characteristics. Only the so-called fibrous thickening of the intima is still doubtful concerning its classification. For the understanding of the severe obliterating arteriosclerosis the knowledge of the early stages is necessary. The disease begins with focal proliferations of smooth muscle cells and a disturbance of permeability of the arterial endothelium. The two cell forms are discussed more in detail and estimated in its significance for the vascular disease. Particularly the lesion of the endothelium nowadays plays an increasing role as causative factor for the development of an arteriosclerosis, since already simple increases of permeability via and edema of the intima may lead to an accumulation of lipoproteins in the vascular wall, also when the lipid level in blood is not increased. At present in clinical practice often the question of the delimitation of an obliterating arteriosclerosis from other arteriopathies leading to a vascular obstruction arises. Since a part of these diseases is to be diagnosed by biopsies of the arteries, the histological differential diagnosis of the most important inflammatory arterial diseases is discussed.

Aging↗
PubMed1980

[Lipid lowering treatment and regression of arteriosclerosis (author's transl)].

The pathogenesis of arteriosclerosis is unknown. As etiological factors which are associated with early development of arteriosclerosis hyperlipemia, cigarette smoking and hypertension are undisputed. More recently studies which show substantial pointers to regression of arteriosclerosis have become more numerous. It has been demonstrated by animal experiments that arteriosclerotic changes can be induced by a diet rich in cholesterol and furthermore can be brought to remission by low fat feeding and/or lipid lowering substances. Indirect pointers to regression, slower or no progressiveness of arteriosclerosis in man have been provided by autopsy findings and epidemiological studies. It has also been recorded angiographically that arteriosclerotic changes can be made to regress by a lipid lowering treatment.

Animals↗
PubMed1978

[Possibilities of prevention and therapy of arteriosclerosis by influencing hemostatic functions].

Thrombotic processes play a role not only as a sequel of arteriosclerosis, but also for its pathogenesis. Under this aspect a pharmacological regulation of the course of the reaction of thrombpcytes, the blood coagulation and the fibrinolysis gets significance. The prevention of the formation of fibrin by well-known anticoagulants, such as coumarines and heparin, seems little suited for a prophylaxis of arteriosclerosis. By a pharmacological regulation of the reaction of the blood platelets which are decisive for the initial phase of the formation of thrombi new possibilities for an intervention into the pathomechanisms of arteriosclerosis are the result. Her also realizations concerning the prostaglandin metabolism of the blood platelets and of the wall of vessels can be evaluated. The activation of fibrinolysis by means of the hitherto introduced fibrinolytics, such as streptokinase and urokinase, is used above all for the treatment of acute thrombi. In the sense of a prevention of arteriosclerosis the activation of the endogenic fibrinolysis with the help of indirect fibrinolytics, which effect a liberation of the activators of fibrinolysis localised in the wall of the vessels, is a hopful way.

Anticoagulants↗
PubMed1995

Up-regulation of endothelin-1 mRNA and peptide expression in rat cardiac allografts with rejection and arteriosclerosis.

Acute and chronic rejection are frequent and significant complications of cardiac transplantation, and graft arteriosclerosis is the leading cause of death beyond the first year after transplant. Levels of endothelin-1 (ET-1) are elevated in plasma of patients with cardiac allografts and those with symptomatic vascular atherosclerosis, but little is known about the role of ET-1 in these processes. This study examined intragraft ET-1 expression in rat cardiac models of acute rejection and chronic rejection associated with graft arteriosclerosis. Corrected ET-1 gene transcript levels were measured with a [32P]dCTP reverse transcription polymerase chain reaction assay normalized with glyceraldehyde-3-phosphate dehydrogenase, and the gene product was evaluated by immunohistology with a monospecific anti-ET-1 antibody at different time points after transplant. ET-1 mRNA levels were significantly increased in acutely rejected (Wistar-Furth rat cardiac allografts transplanted into Lewis rat recipients) and chronically rejected (Lewis allografts transplanted into F344 recipients) vascularized cardiac allografts as compared with isograft controls. In acutely rejected allografts, peak expression occurred on day 5 after transplant. In chronically rejected allografts, the increase in ET-1 mRNA was sustained on days 7, 28, and 75. In both acutely and chronically rejected allografts, ET-1 mRNA upregulation was not seen in host spleens or paired host hearts. Immunohistological analysis confirmed that the bulk of ET-1 peptide expression was localized to mononuclear cells that diffusely infiltrated the graft interstitium (acute rejection and early chronic rejection) and accumulated within the neointima of chronically rejecting hearts with arteriosclerosis. These observations, taken together with in vitro data showing that ET-1 production is stimulated by certain cytokines, indicate that the allogeneic stimulus within rejecting vascularized cardiac allografts, presumably cytokine mediated, leads to significant intragraft up-regulation of ET-1 mRNA and peptide expression. The local up-regulation of this vasoactive and mitogenic peptide within acutely and chronically rejected cardiac allografts suggests that ET-1 may be involved in the development of graft arteriosclerosis.

Animals↗
PubMed1995

Ischemia-induced transplant arteriosclerosis in the rat.

The effect of cold graft ischemia time on the development of transplant arteriosclerosis was investigated. Aorta grafts from DA or PVG rats were stored in a cold perfusion solution for 1, 4, or 24 hours before being orthotopically transplanted to PVG recipients. After observation times ranging from 2 to 8 weeks, the grafts were examined for various cell populations. Regional changes in the intima and media layers were measured by using an image analysis system. The arteriosclerosis-like changes seen in syngeneic grafts with the longest ischemia time could be almost as prominent as those seen in the allogeneic transplants. The magnitude of the regional intima changes in the syngeneic group correlated well with the ischemia time and in the allogeneic group with the observation time. The cell composition found in the intima and media of the allogeneic vessels consisted of macrophages, T-lymphocytes, MHC class II-expressing cells, and smooth muscle cells, whereas the syngeneic grafts contained almost exclusively smooth muscle cells and macrophages. We therefore conclude that the damage due to prolonged cold ischemia time is sufficient to cause pronounced graft arteriosclerosis. The pathophysiological mechanism leading to ischemia-induced arteriosclerosis is different from the one seen in the allogeneic situation.

Animals↗
PubMed1982

Fatty acid composition of adipose tissue, blood, lipids, and glucose tolerance in patients with different degrees of angiographically documented coronary arteriosclerosis.

Forty-eight patients with symptoms of angina pectoris were studied for adipose tissue fatty acid composition and cardiovascular risk factors while hospitalized for selective coronary angiography. Patients with manifest diabetes mellitus and deviations form the "normal" customary diet were excluded. Pairwise comparison between the groups with absent, slight, moderate, and severe coronary arteriosclerosis showed reasonable comparability for age, relative body weight, and skinfold measurements. The proportion of smokers, but not of hypertensives, showed a significant positive relationship with the degree of arteriosclerosis. Serum cholesterol was similar in all four groups, while triglycerides were clearly, but not significantly (P greater than 0.05) higher in patients with coronary arteriosclerosis. The oral glucose tolerance test (OGTT) index was significantly higher in moderate and severe disease. Significantly higher proportions for palmitic acid lower proportions for linoleic acid were also found in these two groups. Multiple linear regression analysis showed a positive association with coronary arteriosclerosis for: OGTT index greater than palmitic acid greater than arachidonic acid greater than triglycerides. The close negative association between the proportion of stearic acid in adipose tissue and coronary heart disease observed in two previous studies could not be confirmed. On the basis of the present study, stearic acid correlates with age rather than with arteriosclerotic disease.

Adipose Tissue↗
PubMed1998

Association between the degree of platelet-derived growth factor-A chain mRNA expression and coronary arteriosclerosis in the transplanted heart.

Although intimal and medial proliferation of smooth muscle cells is recognized as one of the key mechanisms in the development of graft coronary arteriosclerosis, the role of platelet-derived growth factor (PDGF) in this process is still uncertain, because of the undetermined pathogenesis of graft coronary arteriosclerosis (GCA). In the present study, the correlation between the extent of GCA and the degree of PDGF-A chain expression in cardiac grafts was investigated in 21 rats with GCA of varying extent. Lewis rats underwent heterotopic heart transplantation from Wistar King donors and were treated with cyclosporine A (10 mg/kg/day) (n = 7), 15-deoxyspergualin (5 mg/kg/day) (n = 7), or Multiglycosidorum tripterygii (MT) (30 mg/kg/day) (n = 7). Histological evaluations of coronary arteriosclerosis, as well as Northern blot analysis of graft PDGF-A chain expression were made, 60 days after transplantation. Graft coronary arteriosclerosis of varying extent was observed among the 21 transplanted hearts. Significant correlations were found between the PDGF-A chain mRNA expression of cardiac allograft and the grade of arterial intimal thickening (Spearman's r = 0.76, P < 0.005) as well as the incidence of diseased vessels (r = 0.82, P < 0.001). The PDGF-A chain mRNA expression of the cardiac allograft is associated with the extent of GCA, indicating that PDGF-A plays an important role in the development of GCA.

Animals↗
PubMed1998

Noninvasive assessment of transplant-associated arteriosclerosis.

BACKGROUND: Transplant-associated arteriosclerosis is the major limitation to long-term survival in the cardiac transplant recipient, and annual surveillance angiography is used in many centers to monitor its progression. Noninvasive methods would be preferable because angiography is invasive, costly, and insensitive; however, the reliability of such methods has been questioned. METHODS: All publications relating to the assessment of the cardiac allograft by noninvasive testing were identified through MEDLINE and a review of references from the published literature on transplant-associated arteriosclerosis. RESULTS: Resting and stress ECG, radionuclide scintigraphy, echocardiography, and positron emission tomography have all been used in cardiac transplant recipients with variable results. Most techniques are insensitive, but this limitation may be improved with pharmacologic stress imaging like dobutamine echocardiography. Although insensitive, some methods have good specificity (i.e., radionuclide scintigraphy). The noninvasive measurement of absolute coronary blood flow is promising as a specific and sensitive technique but is limited by availability and cost. CONCLUSIONS: In general, noninvasive techniques to assess transplant-associated coronary arteriosclerosis are limited by variable sensitivity and specificity. However, certain methods, such as dobutamine echocardiography and radionuclide scintigraphy, can provide important adjunctive physiologic information to angiography. Such techniques can therefore help to guide the care and treatment of the cardiac transplant recipient with allograft coronary arteriosclerosis.

Coronary Angiography↗
PubMed2003

Platelet-derived growth factor receptor inhibition reduces allograft arteriosclerosis of heart and aorta in cholesterol-fed rabbits.

BACKGROUND: Crosstalk between pro-inflammatory cytokines and platelet-derived growth factor (PDGF) regulates smooth-muscle-cell proliferation in cardiac-allograft arteriosclerosis. In this study, we tested the effect of STI 571, a novel orally active protein tyrosine kinase (PTK) inhibitor selective for PDGF receptor (PDGF-R) on transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. METHODS: Cardiac allografts were transplanted heterotopically from Dutch Belted to New Zealand White rabbits. A 0.5% cholesterol diet was begun 4 days before transplantation. Recipients received STI 571 5 mg/kg per day or vehicle intraperitoneally throughout the study period of 6 weeks. Cyclosporine A was given as background immunosuppression. RESULTS: In cardiac allografts of vehicle-treated rabbits, 76.2+/-2.1% of medium-sized arteries were affected by intimal thickening, and the percentage of arterial occlusion was 45.0+/-5.0%. Treatment with STI 571 reduced the incidence of affected medium-sized arteries to 41.2+/-8.1% (P <0.05) and the arterial occlusion to 27.6+/-5.0% ( P<0.05). In addition, we observed that STI 571 treatment reduced intimal lesion formation in proximal ascending aorta of transplanted hearts from 72.3+/-19.9 to 12.7+/-1.9 microm ( P<0.05). Our results also show that STI 571 significantly inhibited accelerated arteriosclerosis in medium-sized arteries of recipients' own hearts. CONCLUSIONS: The results of the present study suggest that PDGF-R activation may regulate the development of transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. Thus, PTK inhibitors may provide new strategies for prevention of these fibroproliferative vascular disorders.

Animals↗
PubMed2000

Mouse model of transplant arteriosclerosis: role of intercellular adhesion molecule-1.

Transplant-accelerated arteriosclerosis in coronary arteries is the major limitation to long-term survival of patients with heart transplantation. The pathogenesis of this disease is not fully understood. Herein, we describe a simplified model of artery allografts in the mouse that allows us to take advantage of transgenic, knockout, or mutant animals. Common carotid arteries or aortic vessels were end-to-end allografted into carotid arteries between C57BL/6J and BALB/c mice. Neointimal lesions were observed as early as 2 weeks after surgery and had progressed at 4 and 6 weeks postoperatively. The lumen of grafted arteries was significantly narrowed due to neointima hyperplasia 4 weeks after transplantation. Using this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of transplant arteriosclerosis in ICAM-1-deficient mice. Neointimal lesions of artery grafts from ICAM-1 -/- C57BL/6J to BALB/c mice were reduced up to 60% compared with wild-type controls. MAC-1 (CD11b/18)-positive cells adhering to the surface of ICAM-1 -/- artery grafts were significantly less as identified by en face immunofluorescence, and these positive cells were more abundant in intimal lesions of artery grafts in wild-type mice. Furthermore, the major cell component of neointimal lesions 4 weeks after surgery was found to be alpha-actin-positive smooth muscle cells, which were significantly reduced in lesions of ICAM-1 -/- artery grafts. Thus, this model has been proven to be useful for understanding the mechanism of transplant arteriosclerosis. Our findings demonstrate that ICAM-1 is critical in the development of allograft arteriosclerosis via mediation of leukocyte adhesion to, and infiltration into, the vessel wall.

Actins↗
PubMed2003

Angiopoietin-1 protects against the development of cardiac allograft arteriosclerosis.

BACKGROUND: Angiopoietin (Ang)-1 is an angiogenic growth factor that counteracts the permeability and proinflammatory effects of vascular endothelial growth factor and other proinflammatory cytokines. Recently, we demonstrated that vascular endothelial growth factor enhances cardiac allograft arteriosclerosis. Here, we studied the roles of Ang1, its natural antagonist Ang2, and their receptor Tie2 in rat cardiac allograft arteriosclerosis. METHODS AND RESULTS: Heterotopic cardiac allografts and syngrafts were transplanted from Dark Agouti (DA) to Wistar-Furth rats and from DA to DA rats, respectively. Immunohistochemistry disclosed that only a few mesenchymal cells expressed Ang1 in normal hearts and syngrafts, whereas no immunoreactivity was found in cardiac allografts undergoing chronic rejection. Ang2 and Tie2 immunoreactivity was induced mainly in capillaries and postcapillary venules in chronic allografts when compared with syngeneic controls, but no immunoreactivity was found in arterial endothelium. Intracoronary perfusion of cardiac allografts with a clinical-grade adenoviral vector encoding human Ang1 (Ad.Ang1) protected against the development of allograft arteriosclerosis. Ad.Ang1 perfusion reduced Ang2 expression in microcirculation, the numbers of graft-infiltrating leukocytes, and the level of immunoactivation and interstitial fibrosis, as well as both the incidence and intensity of intimal lesions. Ad.Ang1 perfusion also increased CD34+ stem cell counts in peripheral blood. CONCLUSIONS: Our findings suggest that the antiinflammatory properties of Ang1 may offer an entirely new therapeutic approach to prevent cardiac allograft arteriosclerosis.

Adenoviridae↗
PubMed1991

Calcium--a neglected key factor in arteriosclerosis. The pathogenic role of arterial calcium overload and its prevention by calcium antagonists.

Using specific calcium antagonists as experimental tools, both the physiological messenger and current carrying function of calcium ions as well as their pathogenetic potencies could be elucidated. Notably, excess intracellular calcium signalling and intra- and extracellular calcium overload turned out to be pathogenetic principles of general importance. In this context, progressive calcium overload of arteriosclerotic vascular walls and the antiarteriosclerotic effects of calcium antagonists, deserve particular interest. In fact, with the help of calcium antagonists, arterial calcium overload as decisive component of various types of experimental arteriosclerosis became accessible to a direct therapeutic intervention. According to their responsiveness to calcium antagonists, two pathophysiologically different types of experimental coronary plaques could be characterized: (1) The calcium type, i.e. coronary calcinosis of vitamin D3-intoxicated rats highly sensitive to calcium antagonist treatment, (2) the cholesterol type, represented by coronary atheromata of cholesterol-intoxicated rabbits; this primary coronary cholesterol accumulation could not be inhibited by calcium antagonists. The formation of conventional human coronary artery plaques is characterized from the very early lesion onwards by a progressive local uptake of calcium, finally leading to lethal consequences. Conversely, the analysis of the mural cholesterol does not allow to discriminate arteriosclerotic from normal coronary artery segments. Thereby, conventional human coronary plaques typically represent a calcium-dominated type of human arteriosclerosis and differ widely from plaques produced in cholesterol-fed rabbits. The results indicate the decisive pathophysiological role of calcium and calcium overload in both calcium-dominated types of experimental arteriosclerosis and conventional human coronary artery plaques. Moreover, the antiarteriosclerotic effects of calcium antagonists are demonstrated to be based--in various types of experimental arteriosclerosis--on the inhibition of intra- and extracellular calcium overload of arterial walls evoked by various risk factors (vitamin D3 intoxication, hypertension, nicotine, diabetes).

Animals↗
PubMed1995

[Is elevated cholesterol the cause of arteriosclerosis?].

In post mortem studies the alterations produced by arteriosclerosis present a panorama of structural changes that defies the determination of an orderly sequence of events (Netter). Proliferation of fibromuscular vascular wall cell elements and over-production of extracellular matrix is quantitatively predominant. Lipid dispositions comprise less than 5% of the average plaque volume. Arteriosclerosis induced experimentally by cholesterol feeding and vessel wall traumatisation shows dependency in plaque composition from cholesterol feeding. The resulting vessel lumen narrowing is predominantly caused by overproliferation and equal with and without cholesterol feeding. The vision of arteriosclerosis as a "Proliferation disease" therefore appears more adequate than that as a "cholesterol storage disease". When patient groups are separated from coronary arteriography into those with normal coronary arteries and into those with coronary arteriosclerosis differences in cholesterol values are found below the age of 50 years, while above the age of 60 years no difference exists. In all groups the overlap is large and the individual risk can not be determined on the base of cholesterol levels. Between extend of angiographic changes and plasma lipid levels no correlation exists. Angiographic progression of disease which is closely correlated with clinical progression is independent of plasma cholesterol levels determined at the beginning of the observation period. The rate of restenosis after PTCA has been found to be independent of plasma cholesterol levels and can not be influenced by cholesterol lowering. In the report from the NHLBI on more than 600 000 individuals total mortality was independent from plasma cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[An experimental study of coronary arteriosclerosis after heart transplantation].

The purpose of this study is to evaluate the effects of Cyclosporine (CsA), FK-506 (FK) and 15-Deoxyspergualin (DOS) on coronary arteriosclerosis after rat heart transplantation. Three groups of Lewis rats (n = 7, each) received heterotopic heart transplants from F-344 donors and were treated with CsA (Group Cs), FK (Group FK) and DOS (Group DOS) intraperitoneally. All rats were sacrificed 60 days later and assessed microscopic grading score (GS) of rejection and arteriosclerosis, and measured serum lipid. There was no significant difference in the GS of rejection but the GS of arteriosclerosis in the groups Cs was significantly higher than the group DOS (1.71 +/- 0.24 versus 1.11 +/- 0.34, p < 0.01). Triglyceride in the groups Cs was significantly higher than the group FK and group DOS (99 +/- 23 versus 66 +/- 21, 56 +/- 30 mg/dl, p < 0.02), and LDL in the group Cs and group FK was significantly higher than group DOS (104 +/- 17, 81 +/- 23 versus 31 +/- 17 mg/dl, p < 0.01). We concluded that DOS had a superior protective effect against coronary arteriosclerosis after heart transplantation and it may depend on the different mechanism of immunosuppression and lipid metabolism abnormality causing by immunosuppressants.

Animals↗
PubMed1977

Do risk factor interventions prevent or reverse arteriosclerosis?

We have attempted to summarize the current controversies regarding risk factors and preventive measures for control of arteriosclerosis and coronary heart disease. Recognizing that the genesis and development of the disease process are extremely complex and the basic knowledge is limited, it is not likely that conclusive answers to questions will be forthcoming soon which will provide more effective preventive or therapeutic measures. It might be desirable to institute educational and control program aimed at curtailing, at a young age, known AS risk factors such as heavy smoking, particularly if the family history indicates severe risk. Few will question the normal approaches to the treatment of complications of coronary heart disease by control of hypertension, elevated cholesterol, and smoking. However, great caution must be exercised when trying to institute large scale modifications in prevailing life patterns, particularly when based on indefinite risk factor studies and in the face of potentially profound and frequently unknown consequences. The unknowns of atherosclerotic heart disease risk factors, coupled with uncertainties and even doubts about protracted and expensive population studies, lead us to propose an emphasis on alternate selective approaches. We strongly believe that fundamental to progress in the field of arteriosclerosis is an amplification of preventive research efforts with stronger attention focused upon influencing the atherosclerotic processes within the arterial wall. But, more immediately, we urge systematic gathering and careful evaluation of patient data in particular population subsets which exhibit and accelerated mode of arteriosclerosis. Comparative studies of patients, particularly twins, families, and ethnic populations with redilection to early or accelerated arteriosclerosis may be extremely rewarding. Our repeated review of the enormous literature suggests that worldwide collaboration is needed to perfect more meaningful protocols as well as to correlate and critically evaluate existing data provided by population studies of this insidious disease process which represents an evermounting burden to society.

Adult↗