Vasoactive alterations in lower limb subcutaneous resistive arteries from Caribbean patients with atherosclerosis

OBJECTIVE: This study was performed to investigate the endothelium-dependent relaxation and contractile responses to endothelin-1 in subcutaneous resistive arteries from Caribbean patients with advanced atherosclerotic femoro-crural arterial disease. DESIGN AND METHODS: Small subcutaneous arteries (inner diameter 200 um) from control subjects (n=8) and atherosclerotic patients (n=8) were dissected from fat biopsies obtained at routine vascular surgery and mounted in vitro on a wire-myograph measuring parietal tension under isometric conditions. RESULTS: Acetylcholine-induced relaxation (10-6 M) was significantly reduced in pre-contracted arteries from atherosclerotic patients (24 + or - 16 percent vs 17 percent in control, p<0.001). Smooth muscle relaxation to sodium nitroprusside was comparable in both groups. Contractions elicited by endothelin-1 (10-9 M) were significantly lower and almost suppressed in both the atherosclerotic group (1.2 + or - 0.8 Kpa) and in the hypertensive subgroup of control subjects (n=4, 1.2= 0r - 1.2 Kpa) comparatively to normotensive control subjects (12.3 + or - 6.9 Kpa, p<0.001). Contractile responses induced by endothelin-1 at higher concentrations (10-8 - 10-7 M), noradrenaline and hyperosmolar potassium were comparable in both groups. CONCLUSIONS: These data suggest a specific impairment of both endothelium-dependent relaxation and contractility in lower limb subcutaneous resistive arteries from Caribbean patients with atherosclerotic femoro-crural arterial disease. These changes in vessels which largely determine proximal vascular resistance may contribute to ischaemic complications in this vascular bed including skin ulcerations and gangrene.(Au)

Apolipoprotein-E polymorphism in Curacao newborns - abstract

Apolipoproteins (apo)E (2) and E (4) are associated with disease development at later age. In Caucasians, homozygosity for apo-E (2) (apo-E/E) occurs in over 80 percent of patients with familial dysbetali-poproteinaemia (prevalence: 0.04 percent). Subjects with apo-E/E have higher cholesterol, both LDL and total, than subjects with the common apo-E/E genotype. High prevalence of apo-E/E in patients with Alzheimer's disease connects apo-E genotype to neuro-degenerative disease development. Little is unknown on apo-E polymorphism in Black populations. Using molecular biological techniques, we determined apo-E genotypes of 234 consecutive cord blood samples in Curacao (The Netherlands Antilles). Forty per cent of babies born during the period of November 1992 - February 1993 were screened. Found and expected Curacao apo-E genotype distributions were not significantly different. Found Curacao apo-E genotype distribution was not different from Dutch, but differed in Nigerians and US-Blacks (p<0.0001). Genetic differences between Curacao and Nigeria/US-Blacks agree with different haemoglobin C prevalences. It remains to be established to what extent apo-E polymorphism contributes to atherosclerotic and neurodegenerative disease development in Curacao (AU)

Diabetic nephropathy is not preventable - abstract

Renal failure in diabeties mellitus is becoming the commonest cause of end-stage renal disease (ERSD) in developed and developing countries. While ERSD occurs in about 35 percent of patients with insulin-dependent diabetes mellitus (IDDM), it occurs generally in about 15-60 percent with non-insulin-dependent diabetes mellitus (NIDDM), depending on ethnicity. Since most of the diabetes are NIDDM, it follows that most of these patients developing renal failure and requiring dialysis are NIDDM. When significant proteinuria begins, usually after about 15-20 years of NIDDM or IDDM, renal function will fall steadily and the patient will require dialysis in 3-5 years or sooner. The proteinuric patients also have a 20-40-fold increase in cardiovascular mortality. About one-quarter of the patients who have negative routine urinary protein dipstick tests will have sub-clinical amounts of urinary albumin (30-300 mg/24 hr), so-called microalbuminuria (MA). This has recently been correlated with a very high incidence of microvascular disease. This MA predicts about a 20-fold chance of the patient developing clinical proteinuria and a high chance of ERSD. The accumulated evidence suggests that a common pathogenic mechanism may exist for microalbuminuria, diabetic nephropathy, atherosclerosis and obesity. Obesity seems to be related to all of these factors in that it has been associated with insulin resistance, hypertension and so dium retention, atherosclerosis and hyperlipidaemia (HL). NIDDM patients are almost always obese and they always have insulin resistance, which improves with weight loss. There is growing clinical evidence of hereditary influence in NIDDM, HL, and hypertension with the clustering of diabetic nephropathy in these high-risk families. These data show that genetic factors may well play a major role, and it is therefore understandable that we may have difficulty in altering the already genetically charted course of proteinuria, hypertension, HL, and NIDDM (AU)

Renal pathology in diabetes mellitus - abstract

The morphological changes in both insulin-dependent and non-insulin-dependent diabetes mellitus (IDDM and NIDDM) are indistinguishable. The earliest pathological changes are enlarged glomeruli due to hypertrophy seen mainly in IDDM patients. There is also an increase in total volume of both basement membrane (BM) and capillary lumen. A second peak of glomerular hypertrophy occurs late in the disease when overt pathological changes are established. At this, many glomeruli are comprised and the open, functioning glomerulii will show a three-fold increase in size. The pathognomonic change in diabetic nephropathy is nodular glomerulosclerosis or nodular intercapillary glomerulosclerosis (Kimmelstiel-Wilson lesion) which is characterised by enlargement of mesangium due to increase in mesangial matrix. This is associated with diffuse thickening of the capillary wall which is due to increased BM material. A diffuse lesion may be considered specific after ruling out all the other causes of thickened BM, i.e. immune-complex glomerulonephritis, anti-glomerular basement membrane antibody disease, etc. The exudative and capsular drop lesions are not specific for diabetes mellitus but can be considered to be highly suggestive lesions. There is hyaline arteriolosclerosis, involving both afferent and efferent arterioles. The only pathognomonic tubular lesion (Armanni-Ebstein lesion) is a rare finding, and is found in the straight portion of the proximal convoluted tubules in which tubular cells contain glycogen. The patients with the nephropathic syndrome may show lipid-filled proximal tubules. In the late stages, there are non-specific atrophic changes with thickening of the basement membrane. There are no specific gross features of the kidney in diabetes mellitus. It may be enlarged, normal or granular contracted. The subscapular surface may either be finely or coarsely granular with focal depressed scars. The cut surface may show thinning of the cortex, loss of the corticomedullary junction and prominent blood vessels. Papillary necrosis is uncommon (AU)

Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations

Two populations of immigrants to London and to the West Indies from the Indian subcontinent have greater than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3 percent of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian population.(AU)

Dietary concepts in diabetes

The importance of diet in the management of diabetes mellitus is well recognized yet many diabetics do not follow their diets. There are a variety of reasons for the failure of dietary management. These include a lack of motivation, inadequate instructions or understanding, a monotonous choice of foods and unrealistic expectations. This paper will present the concepts of diet therapy and those objectives and strategies which are currently generally accepted in the dietary management of diabetes (AU)

Variation in human aortic fatty streaks among geographic locations

Histological features of aortic fatty streaks were examined in male subjects aged 10-39 from Guatemala, Jamaica Negro, Durban Bantu, New Orleans Negro, New Orleans white, Lima and Santiago. These groups were selected from the 19 available in the IAP (International Atheroschlerosis Project) because they represented the greatest contrasts between the extent of fatty streaks in the young and raised lesions in the elders. Among these seven groups the extent of raised lesions in the older subjects was significantly but weakly correlated with the type of fatty streaks in the young as measured by lesion thickness, content of demonstrable lipid, numbers of foam and spindle cells. The severity of leukocytic infiltration and prevalence of foci of necrosis in fatty streaks however, correalted strongly with raised lesions (rank r=0.90). We interpret this to imply that the presence of leukocytes and of foci of necrosis in the fatty streak marks its propensity to progress into raised lesions. If this formulation is correct, then the presence of both features in the histology of fatty streaks could be used as a marker in future studies of factors bearing upon the emergence of raised lesions out of fatty streaks (AU)

Diet and mortality from malignant disease in 32 countries

W.H.O. mortality figures for 26 different types of malignant disease taken from 32 countries were correlated with data on the composition of the diet, as well as with certain indices reflecting aspects of general development, for those of the 32 countries for which they were available. For a majority of tumors the results were negative, but most showed a strong association with dietary factors. These included a positive correlation with the national consumption of fats and oils, total calories, and sugar, and a negative correlation with cereal consumption. For malignant tumours the rectum, breast, prostate, skin, nervous system, and bladder, and for leukaemia, lymphosarcoma and multiple myeloma, the probability of this association occurring by chance was less than 1 in 1,000. In seven cases the relationship with dietary factors was of a similar order to that of arteriosclerotic and degenerative heart disease. For all of the 18 separate types associated with diet, the correlation was higher than with the indices of general development,i.e., gross national product, newsprint consumption, percentage of the population engaged in agricultue and infant mortality. (AU)

Fatty streaks in the coronary arteries and aorta

We have analyzed the extent of fatty streaks in the coronary arteries and aortae of young persons 10 to 39 years old from 19 geographic and ethnic groups. Fatty streaks in the aorta increase rapidly in succeeding age groups during the second decade of life, and in some groups during the third decade. There after they tend to diminish in extent or remain at approximately the same level. Fibrous plaques and other advanced lesions approach similar degrees of extent 20 years or more later. The extent of aortic fatty streaks in youth does not predict the extent of aortic raised lesions later in life on agroup basis. Fatty streaks in the second and the third decades of life, and show no tendency to regress at any age. The mean extent of coronary artery fatty streaks in young persons appears related to the mean extent of raised lesions in the same population at middle age in non-Negro groups. These data are consistent with the hypothesis that advanced atherosclerotic lesions develop by progression and transformation of fatty streaks. However, the degree to which the transformation takes place appears to vary among arteries and among racial groups. (AU)

Distribution of cerebral atherosclerosis by geographic location, race, and sex

The cerebral arteries (common carotid, internal carotid, vertebral, middle cerebral, and basilar arteries) were examined from 1547 autopsied persons in five countries (Norway, Guatemala, United States, Jamaica, and Chile). Subgroups comparisons were made using a basal group of cases from which were excluded all persons with coronary heart disease, peripheral arterial disease, other atherosclerotic complication, hypertension, and diabetes. The prevalence and mean extent of atherosclerotic lesions increase in each succeeding age group. Lesions appear to develop later in life in the cerebral arteries than in the aorta and the cerebral arteries than in the aorta and the coronary arteries. Men have more raised atherosclerotic lesions than women. The mean extent of fatty streaks in the cartoid arteries does not differ among age groups from 35 to 69 years of age, nor does it differ among location-race groups. The mean extent of raised atherosclerotic lesions in the carotid arteries increases in each succeeding age group after 35 years of age, and differs among location-race groups.The pattern of development of atherosclerosis in the carotid arteries follows that of the aorta. Fatty streaks appear in the intracranial and vertebral arteries much later in life than they do in the carotid arteries.The mean extent of both fatty streaks and raised lesions increases in each succeeding age group after 35 years of age, and the average involvement of both types of lesions differs among location-race groups. The pattern of development of atherosclerosis in the vertebral and intracranial arteries follows that of the coronary arteries. When location-race groups are ranked by extent of cerebral atherosclerosis, they rank in approximately the same order as when they are ranked by aortic and coronary atherosclerosis. (AU)

Histologic characteristics of coronary artery fatty streaks

The histologic characterictics of a standard site in the left interior descending coronary artery of 304 males between 10 and 39 years of age from seven different populations were examined. These seven location-race groups were ranked in the same order as the ranking based upon mean extent of raised atherosclerotic lesions in the coronary arteries and aorta to establish the tendency of each group to develop advanced atherosclerosis. Muscloelastic intimal thickening in the earlier decades does not predict the likelihood to develop severe atherosclerosis. Amount of intimal lipid and degree of cellular infiltration do predict the disposition to develop severe atherosclerosis later in life. Therefore, increased intimal lipid and cellular infiltration characterize coronary artery fatty streaks that are associated with their conversion to fibrous plaques. Necrosis of lipid-containing cells may release intracellular lipid into the extracellular space and thereby incite cellular infiltration and sequelae. (AU)

Atherosclerosis in persons with selected diseases

Comparison has been made of measures of coronary and aortic atherosclerosis in autopsied persons having five selected diseases (lung cancer,stomach cancer, other cancer, cirrhosis of the liver, and tuberculosis) with similar measures in control cases. There appears to be a slight but not significant tendency for lung cancer to be associated with more severe atherosclerosis within age-location-race subgroups. The tendency is strongest in the abdominal aorta. None of the other four diseases appears to be associated with increased or decreased severity of atherosclerosis in comparison with the control groups.(AU)

Distribution of coronary and aortic atherosclerosis by geographic location, race, and sex

Cooperating pathologists in different countries collected 23,207 sets of coronary arteries and aortae, according to a standard protocol. A central laboratry staff stained the arteries with Sudan IV, and a team of pathologists graded the atherosclerotic lesions. A basal group of cases which died from accidents, infections, cancer, and selected miscellaneous causes was extracted in order to compare atherosclerosis among the different geographic, racial, and sex subgroups. Even the most homogeneous subgroups (same location, sex, age, and race) vary greatly in extent of advanced atherosclerotic lesions. The 19 location-race groups differ significantly in extent of raised lesions. The abdominal aorta and the left anterior descending coronary artery have more atherosclerosis than other arteries. Within most location-race groups, coronary arteries of men have more raised lesions than the coronary arteries of women. Aortae of men in some groups have slightly more, and in other groups slightly less raised lesions than the aortae of women. Negro groups show little or no sex difference in either the coronary arteries or the aorta. Ranking of the 19 location-race groups by raised atherosclerotic lesions is similar, regardless of lesion measure (fatty streaks excepted), sex, artery, or age group. New Orleans white and the Oslo group rank highest; Bogota, Sao Paulo Negro, Guatemala, and Durban Bantu groups rank lowest. With few exceptions, ranking these groups by raised lesions corresponds closely with ranking them by coronary heart disease mortality rate. (AU)

Some factors influencing the development of atherosclerosis: A survey in Jamaica, West Indies

Using a quantitative method of assay the degree of atherosclerosis of the aorta, coronary arteries and cerebral arteries has been determined in a large, predominantly Negro, autopsy series in Jamaica, West Indies. There is a progressive worsening of the disease with age but there are considerable individual variations at all ages. The aorta, coronary and cerebral arteries are affected in that order in time and severity. Atherosclerosis is generally more severe in men and hypertension accentuates the disease, especially in women after the menopause. Hypertension is more important than atherosclerosis in causing cerebrovascular disease in Jamaica. Diabetes alone does not seem to influence adversely the development of atherosclerosis except in combination with hypertension. Evidence for the effect of malignant disease was inconclusive. Severe degrees of atherosclerosis are encountered in the Jamaican Negro but the supposed complications are relatively uncommon. This supports the view that factors other than initial disease, principally those connected with thrombosis, are concerned in the pathogenesis of ischaemic vascular disease. (AU)

Some further observations on atherosclerosis in Jamaica (abstract only)

Preliminary studies in Jamaica indicated that the incidence of athero-sclerosis of the aorta showed a similar pattern to that in the United States although the incidence of myocardial infarction, a presumed complication of atherosclerosis, is far lower in Jamaica than in the U.S.A. The study has been extended to include a comparative assay of the coronary arteries and it has been found that the degree of coronary atherosclerosis is significantly greater in comparable age groups in the United States of America than in Jamaica. The implications of this dissociation are discussed. The Jamaican results have been analysed to determine the influence of age, sex, hypertension and diabetes on the disease process (AU)

Geographic differences in the severity of aortic and coronary atherosclerosis

Comparison of aortic and coronary atherosclerosis in the United States, Jamaica, Japan and India demonstrates that after the first two decades of life, there is a greater severity of intimal alteration in the United States than in the other population groups. The 3 foreign populations exhibited much less coronary atherosclerosis and a lower incidence of myocardial infarction. Their diets, too, were of lower caloric content and contained less than half the fat found in the United States diet. In Japan and Jamaica, atherosclerosis proved to be disproportionately more severe in the aorta than in the coronary arteries. Accordingly, appraisals of atherosclerosis limited to the aorta do no provide adequate indexes of geographical variations. A much lower proportion of complicated atheromatous lesions (ulcerated or calcified plaques) accounted for most of the differences observed. While there was a general parallelism between the severity of coronary atherosclerosis and the frequency of myocardial infarction, there were instances of cardiac infarction associated with relatively minor degrees of coronary intimal alteration. These situations indicate that virtually all grossly recognizable intimal lesions may be complicated by thrombosis (Summary)

Atherosclerosis and ischaemic heart-disease: observations in Jamaica

Using a standardised technique, the incidence of atherosclerosis of the aorta at 500 necropsies in Jamaica has been compared with the incidence in published series in which the same method was employed. The predominantly Negro population in Jamaica develops a degree of aortic atherosclerosis similar to that of a mixed population in New Orleans, U.S.A. The incidence of myocardial infarction, however, is much lower in the Jamaican series. Other thrombotic diseases are also rarer in Jamaica. Since there is no constant relation between the incidence of atherosclerosis and the incidence of coronary thrombosis, they are very unlikely to have the same cause. Atherosclerosis may or may not be promoted by a dietetic factor; but, if it is, the same factor can hardly be responsible for the thrombosis which results in ischaemic heart-disease. In aetiological studies the two conditions need to be clearly distinguished. Since advanced atherosclerosis is compatible with health and long life, investigation of the cause of thrombosis is of more immediate concern (AU)

Atherosclerosis of the aorta in Jamaica (abstract only)

As part of a geographical survey of atherosclerosis a method has been used to assess qualitatively and quantitatively the degree of sortic atherosclerosis at routine autopsy. To date 368 cases from all age groups have been studies in Jamaica. A preliminary analysis of the results has been made and compared with similar published series. Contrary to what has been claimed by other authors the Jamaican figures would appear to indicate that there is not necessarily a direct correlation between the degree of aortic atherosclerosis and the liability to the development of the serious sequelae of atherosclerosis such as myocardial infarction. (AU)