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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this article we have focused on the evolving pattern of nutritional management of the person with diabetes. Before the advent of insulin in 1922, it was sufficient to identify a meal plan that would keep people alive until they could be rescued from mortality due to diabetic ketoacidosis (the major killer of the era) by pharmacologic means. Now, the life expectancy of people with diabetes is close to that of the general population and focus has turned to combating the new threats of macrovascular disease and kidney failure. Over recent years the susceptibility of NIDDM patients to macrovascular events has been established and the twofold increase in risk of a heart attack in diabetic men is outshadowed by the four- to fivefold risk in diabetic women and the 13- to 17-fold greater risk in diabetics under the age of 30 years compared with their nondiabetic counterparts. The mechanism behind the susceptibility to macrovascular disease has generated a veritable plethora of investigations focusing on the atherogenic profile of diabetic dyslipidemia. Hyperinsulinemia, insulin resistance, and overtreatment of the diabetic with insulin have been claimed as contributors to the development of premature atherosclerosis. The hallmark of the diabetic dyslipidemia is the tendency to elevated VLDL triglyceride levels and the closely linked reduction in HDL cholesterol. Although there is some controversy on the relationship between triglyceride levels and the incidence of CAD, there is no doubt that HDL is an independent risk factor. It can now be safely said that elevated triglycerides are a risk factor in women and that in men elevated triglycerides constitute a risk factor if accompanied by a reduced HDL level. For these reasons, any approach to nutritional management of the diabetic must attempt not only to normalize glycemia but to make every effort to reduce the atherogenic profile. In the accompanying algorithm (Fig. 4), we consider the risk factors conducive to a reduction in life expectancy and offer a meal plan that is appropriate for the individual with diabetes. For the 80% of NIDDM patients who are obese, a diet with a reduction of 500 to 1000 kcal is in order and this may be achieved by a periodic VLCD. We examined carefully the controversy related to yo-yo dieting and support the notion that its effects in humans are not all that harmful. Ingestion of simple sugars in the high carbohydrate diet has negative effects both on carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The good, the bad, and the ugly in diabetic diets. 131 32

The use of antihypertensive drug treatment has altered the natural history of hypertension. Whereas congestive heart failure, cerebral hemorrhage, and renal failure were the major complications of untreated severe hypertension, myocardial infarction and thrombotic stroke have emerged as major problems in treated hypertensive patients. None of the major therapeutic trials in hypertension have provided evidence that reducing blood pressure reduces the risk of atherosclerotic complications of hypertension. Hypertension certainly aggravates the severity of atheromatous lesions in experimental animals, and may do so in humans. However, atherosclerosis is more closely related to disturbances in lipoprotein metabolism than to other factors. The common finding that serum cholesterol is raised in hypertensive patients may be due to atherosclerosis being the primary lesion, and hypertension a secondary complication rather than hypertension being the primary lesion.
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PMID:Hypertension and vascular disease. 138 98

The endothelium may play a role as a target and mediator of hypertension. Due to its anatomical position, it is very exposed to mechanical forces; as a source of vasoactive material it may participate in increasing peripheral vascular resistance and in promoting local ischaemia in the heart and brain. Morphological and functional changes in the endothelium occur in experimental and human hypertension. However, the severity of the defect and the mechanisms involved among vascular beds and models of hypertension are heterogeneous. Endothelium-dependent relaxations are impaired in the aorta, carotid artery and in cerebral and mesenteric arterioles in hypertension. In the coronary circulation the defect is less pronounced. The mechanisms involve a reduced formation of nitric oxide, an enhanced production of prostaglandin H2 and an impaired responsiveness of vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is controversial; circulating levels appear unaltered except in the presence of renal failure or atherosclerosis. The local vascular production of endothelin, however, may still be increased. The potentiating effects of threshold concentrations of endothelin on the vasoconstrictor response to noradrenaline are enhanced in hypertension. Thus, subtle and distinct endothelial function defects occur in hypertension, but not all vascular beds are similarly affected and different mechanisms contribute. Endothelial dysfunction may contribute to increased peripheral resistance, tissue ischaemia and cardiovascular complications.
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PMID:Heterogeneity of endothelial dysfunction in hypertension. 139 60

The most serious complication of diabetes mellitus is clinical nephropathy. The development of persistent proteinuria (urinary excretion of more than 300 mg albumin/24 hours) implies an extremely high risk of early death. Renal failure is the most frequent cause of death but the mortality of cardiovascular diseases is also increased. Besides the link between albuminuria (nephropathy) and atherosclerosis in coronary arteries, albuminuria is also a predictor of microangiopathy in other organs than the kidneys. The annual incidence of proliferative retinopathy in early nephropathy is 10-15% compared to only 1% in patients without nephropathy. Also signs of cardiomyopathy have been demonstrated in early nephropathy. Further we have described markers of universal endothelial damage in these patients, and we hypothesize that albuminuria not only is a predictor of renal disease but also of widespread vascular disease. Long-term improvement of metabolic control by use of insulin infusion pumps and early antihypertensive treatment seem to stop the further progression of early diabetic nephropathy and to significantly improve the prognosis of clinical nephropathy.
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PMID:Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients. 149 Jun 95

Hypertension is a major risk factor for cardiovascular diseases, including coronary artery disease (CAD), stroke, left ventricular hypertrophy (LVH), congestive heart failure, peripheral vascular disease, renal failure, and aortic aneurysms. It is also a potent promoter of atherosclerosis. Observational studies have shown a linear relationship between a wide range of blood pressures and the risk for CAD and stroke. Clinical trials have indicated that hypertension reduction leads to the predicted reduction in stroke incidence, but that CAD incidence is affected to a lesser extent than predicted. The modest effect of traditional antihypertensive drugs on CAD may be due to several factors, including failure to reverse well-established coronary atherosclerosis, particularly if multiple risk factors are not reduced as well. Metabolic side effects of antihypertensive drugs or excessive lowering of blood pressure leading to inadequate myocardial perfusion, especially in patients with increased left ventricular (LV) mass, also may play important roles. Hypertension is a major cause of renal failure, particularly in black males, but control of the hypertension does not necessarily prevent deterioration of renal function. Increased glomerular pressure is thought to play a causative role in the development of renal failure in hypertensive and diabetic patients. Antihypertensive drugs may have a direct effect on the arterial wall, which may be independent of their antihypertensive action. Beta-adrenergic blockers, calcium antagonists, and angiotensin-converting enzyme (ACE) inhibitors inhibit the development of vascular lesions in response to hypercholesterolemia or to iatrogenic balloon injury, but the clinical importance of these observations remains to be determined.
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PMID:Vascular effects of systemic hypertension. 157 75

Between May 1966 and June 1991, 129 patients underwent surgical repair of thoracoabdominal aneurysms, with an overall 30-day mortality rate of 35%. In 75 operations (58%) performed electively, 11 deaths (15%) occurred, and in 54 cases (42%) of either symptomatic or ruptured aneurysms 34 deaths (63%; p less than 0.001) occurred. No one survived among six patients with preoperative hypotension (less than 90 mm Hg) or cardiac arrest. In 16 patients (12%) the etiology of aneurysms was a result of chronic aortic dissection, and the mortality rate in this subgroup was 44%. In the remaining 113 patients (88%) where the etiology was atherosclerosis, 38 deaths occurred (34%; p = 0.433). Spinal cord ischemia occurred in 25 cases (21%) among 116 patients who survived operation. Partial ischemia occurred in six cases (25%), and complete paraplegia occurred in the remainder. Complete and partial paraplegia occurred in 16 of 42 cases (38%) when all of the thoracic aorta was replaced (Crawford groups I, II) and in 9 of 74 cases (12%) when only the abdominal or lower thoracic aorta was replaced (Crawford groups III, IV; p = 0.016). Other complications included myocardial infarction (14 cases, 11%), respiratory failure (46 cases, 36%), and renal failure (33 cases, 27%). The major prospect for improved early survival of patients with thoracoabdominal aneurysms seems to be early detection and elective repair before the occurrence of symptoms.
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PMID:Thoracoabdominal aneurysm repair: a representative experience. 157 33

Patients with end-stage renal failure (ESRF) on renal replacement therapy are at significantly increased risk of cardiovascular disease. To determine whether altered concentrations of apolipoprotein(a) (apo(a)), the plasminogen-like protein moiety of the atherogenic particle lipoprotein(a), contributed to this increased risk, apo(a) concentrations were measured in 48 non-diabetic patients with ESRF treated by continuous ambulatory peritoneal dialysis (CAPD) therapy and compared with 65 controls. Apo(a) concentration was increased in CAPD patients compared to controls (geometric mean 419 units/l versus 137 units/l; ratio of means 3.06 (95% CI 1.95-4.80). We conclude that CAPD patients have increased apo(a) concentrations which may contribute to their increased risk of cardiovascular disease.
Atherosclerosis 1992 Mar
PMID:Increased serum apolipoprotein(a) in patients with chronic renal failure treated with continuous ambulatory peritoneal dialysis. 159 3

Diabetic patients who develop proteinuria show a marked increase in cardiovascular morbidity and mortality. The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain, in part, obscure. However, there is now evidence that renal disease clusters in families and that genetic factors may be of central importance in determining susceptibility. Predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. Interestingly, fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first clinical signs of renal involvement are the appearance of microalbuminuria and a small elevation in arterial pressure. Mesangial expansion accompanies these changes. Microalbuminuria is associated with abnormalities of lipoprotein profiles and higher Na+/Li+ countertransport rates. The environmental changes brought about by diabetes could lead in susceptible individuals to increased systemic and intraglomerular pressures on the one hand and to mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered, involving reduction in renal function, further hypertension, proteinuria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Risk factors for renal and cardiovascular disease in diabetic patients. 165 64

Chronic renal failure is associated with abnormalities in lipoprotein metabolism that may contribute to premature atherosclerosis and early mortality in patients on dialysis. In previous studies, we found that plasma clearance of radiolabelled low density lipoprotein (LDL) was retarded in nephrectomized guinea pigs left with one-sixth of normal functioning renal mass. To elucidate potential mechanisms of delayed LDL clearance, we compared binding of LDL to hepatic membranes from both normal and uremic guinea pigs. One hundred micrograms of the 8000-100,000 X g hepatic microsomal protein was incubated with 125I-labelled normal guinea pig LDL (10-150 micrograms/mL) for 1 h at 37 degrees C, and the membrane washed and pelleted by centrifugation in a Beckman Ti 42.2 rotor. Parallel incubations with excess unlabelled LDL were done to determine specific binding. LDL specific binding to uremic hepatic membranes was significantly impaired compared with normal ones. The major abnormality, as determined by Scatchard transformation of the binding data, was a reduction of the apparent maximal binding of LDL to uremic membranes, with an average Bmax of 4.1 micrograms/mg protein compared with 6.6 micrograms/mg protein for normal hepatic microsomes. The affinity of LDL for uremic liver membranes was only slightly diminished with a mean apparent Kd of 35.2 micrograms/mL in comparison with 21.8 micrograms/mL for normal liver membranes. These results provide a biochemical explanation for the diminished LDL clearance in uremia and may account for the dyslipidemia of renal failure.
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PMID:Impaired binding of low density lipoprotein to hepatic membranes from uremic guinea pigs. 166 54

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
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PMID:Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease. 166 3


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