Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular complications are the leading cause of mortality in patients with end-stage renal disease (ESRD). The excess cardiovascular risk and mortality is already demonstrable in early renal disease and in patients with chronic renal failure (CRF), with the highest relative risk of mortality in the youngest patients. The high risk for cardiovascular disease (CVD) results from the additive effect of multiple factors, including hemodynamic overload and several metabolic and endocrine abnormalities more or less specific to uremia. CVD includes disorders of the heart (left ventricular hypertrophy [LVH], cardiomyopathy) and disorders of the vascular system (atherosclerosis, arteriosclerosis), these two disorders being usually associated and interrelated. LVH is the most frequent cardiac alteration in ESRD, resulting from a combined pressure and volume overload. LVH in general is an ominous prognostic sign and an independent risk factor for arrhythmias, sudden death, heart failure, and myocardial ischemia. Regression of LVH needs a combined intervention to reduce hemodynamic overload and is associated with improved prognosis and survival. Clinical studies have shown that damage of large conduit arteries is a major contributing factor for the high incidence of congestive heart failure (CHF), LVH, ischemic heart disease (IHD), sudden death, cerebrovascular accidents, and peripheral artery diseases. Damage to large conduit arteries is principally related to highly calcified occlusive atherosclerotic lesions and to stiffening of large capacitive arteries. These two complications are independent risk factors for survival, and improvement of arterial stiffness is associated with better prognosis and survival. The present review summarizes the most recent works dealing with the pathophysiology of CVD and some aspects of the therapeutic approach.
Semin Dial
PMID:Cardiovascular disease in chronic renal failure: pathophysiologic aspects. 1264 70

Growing evidence has been gathered over the last 15 years regarding the role of nontraditional or uremia-related risk factors in the pathogenesis of atherosclerosis in subjects with renal failure. Among those factors, dyslipidemia, inflammation, hyperhomocysteinemia, and oxidant stress have been extensively studied. However, the clinical significance of many of these factors remains controversial in light of reported studies. In this article, the existing evidence regarding the role of uremia-related risk factors in the pathogenesis of atherosclerosis is reviewed, with special emphasis on prevalence, cardiac risk, and management in patients with chronic kidney disease (CKD). Consensus treatment recommendations are provided for risk factors for which there is evidence to support preventive or therapeutic interventions.
Semin Dial
PMID:Uremia-related metabolic cardiac risk factors in chronic kidney disease. 1264 80

Iron-derived reactive oxygen species (ROS) are implicated in the pathogenesis of numerous vascular disorders including atherosclerosis, microangiopathic haemolytic anaemia, vasculitis and reperfusion injury. One abundant source of redox-active iron is haem, which is inherently dangerous when released from intracellular haem proteins. The present review concerns the likely involvement of haem in vascular endothelial cell damage and the strategies used by endothelium to minimize such damage. Exposure of endothelial cells to haem greatly potentiates cell killing mediated by polymorphonuclear leukocytes and other sources of ROS. Free haem also promotes the conversion of low-density lipoprotein to cytotoxic oxidized products. If only because of its abundance, haemoglobin probably represents the most important potential source of haem within the vascular endothelium; free haemoglobin in plasma, when oxidized, can transfer haem to endothelium, thereby enhancing cellular susceptibility to oxidant-mediated injury. As a defence against such toxicity, upon exposure to free haem, endothelial cells up-regulate haem oxygenase-1 and ferritin. Haem oxygenase is a haem-degrading enzyme that opens the porphyrin ring, producing biliverdin, carbon monoxide and a most dangerous product-free redox-active iron. The latter can be controlled effectively by sequestration within ferritin, a multimeric protein with a very high capacity for storing iron. These homeostatic adjustments have been shown to be effective in the protection of endothelium against the damaging effects of exogenous haem and oxidants. The central importance of this protective system was highlighted recently by the discovery of a child diagnosed with haem oxygenase-1 deficiency, who exhibited extensive endothelial damage.
Nephrol Dial Transplant 2003 Jul
PMID:Haem, haem oxygenase and ferritin in vascular endothelial cell injury. 1281 58

Obesity and hyperhomocysteinaemia are found very frequently after kidney transplantation (Tx). They may independently represent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, over a period of 24 months, a total of 118 obese transplant patients [body mass index (BMI) > or =30 kg/m(2)] with hyperhomocysteinaemia. We compared the findings of a new therapeutic regimen at 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with orlistat at a dose of up to 3 x 120 mg/day, statins (pravastatin 10-40 mg), folic acid 5 mg/day and vitamin B6 50 mg/day, and followed-up for up to 2 years. All patients were on a regimen of cyclosporin A and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (P < 0.025) and total homocysteine level (P < 0.001). Long-term therapy was associated with a significant decrease in serum leptin (P < 0.001) and lipid metabolism parameters (P < 0.01). The mean values of serum folate and vitamin B6 also increased significantly (P < 0.01); creatinine clearance, mean blood pressure, proteinuria, lipoprotein(a) and apolipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperhomocysteinaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), long-term diet (IHHD), folic acid and vitamin B6 supplementation, and drugs suppressing digestion or absorption to reduce atherosclerotic and chronic allograft nephrop-athy processes.
Nephrol Dial Transplant 2003 Jul
PMID:Obesity and hyperhomocysteinaemia after kidney transplantation. 1281 77

Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well-being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long-term application.
Ther Apher Dial 2003 Aug
PMID:Low-density lipoprotein apheresis: an overview. 1288 19

Patients that are homozygous for familial hypercholesterolemia (FH) exhibit severe hypercholesterolemia, cutaneous and tendon xanthomas and premature atherosclerosis beginning in childhood. They are resistant to drug therapy and low-density lipoprotein (LDL) apheresis is the practical treatment. Here we review the technique of LDL apheresis treatment, the long-term effects of LDL apheresis, the effect of apheresis on pregnancy, and the drugs that have proven beneficial in patients with homozygous FH. We also record our experiences of treating eight homozygous FH patients using the LDL apheresis treatment. Among the eight patients, one has been free from cardiovascular disease and two patients have each regressed once. In two patients, aortic valve stenosis developed and the other two patients died for acute myocardial infarction. Furthermore, two patients delivered healthy babies in spite of coronary artery disease. Thus, LDL apheresis therapy has the possibility of preventing the progression of atherosclerosis, but the prognosis assessed by long-term observation is still not satisfactory. A recent clinical trial showed some efficacy of the combination therapy of LDL apheresis and atorvastatin for reducing serum cholesterol levels in homozygous FH, suggesting that this combination therapy may be useful for prevention of atherosclerosis in patients homozygous for FH.
Ther Apher Dial 2003 Aug
PMID:Long-term effect of low-density lipoprotein apheresis in patients with homozygous familial hypercholesterolemia. 1288 21

This article summarizes the clinical evidence for low-density lipoprotein (LDL) apheresis to improve prognosis of patients with coronary heart disease. Regarding clinical events or angiographic parameters, most trials have revealed favorable effects on coronary artery disease. In the studies with a clinical endpoint, approximately 50% reduction in incidence of major coronary events was achieved by LDL apheresis. Similarly, in the studies with a angiographic parameter, coronary atherosclerosis was suppressed or regressed by LDL apheresis. The mechanisms of these effects by LDL apheresis are attributed to improvement in coronary flow reserve, which is dependent upon increases in hemo-rheological factor, nitric oxide, vasoactive substances or decrease of oxidized LDL. These new insights into mechanisms will expand the indication of LDL apheresis to other pathophysiological conditions of coronary artery disease and other disorders.
Ther Apher Dial 2003 Aug
PMID:Low-density lipoprotein apheresis in the prevention of recurrent coronary heart disease: a review. 1288 23

Low-density lipoprotein apheresis (LDLA) leads to an improvement of microcirculation during the very early stages of treatment, and continued treatment may produce antiatherogenic effects in patients with peripheral arterial disease (PAD). Suppression of oxidative stress, improvement of endothelial functions and alteration in the action of vasoactive compounds may occur with the improvement of the rheological property of blood as a result of aggressive removal of atherogenic factors including LDL, possibly resulting in the suppression of development of atherosclerosis. As these effects of LDLA may ameliorate not only PAD but also ischemia in other organs, it is suggested that repeated LDLA prevents the progression of atherosclerotic diseases and probably improves the long-term prognosis of patients with PAD.
Ther Apher Dial 2003 Aug
PMID:Changes in oxidative stress and microcirculation by low-density lipoprotein apheresis. 1288 25

The adhesion molecules on the leukocytes and the endothelial cells mediate interaction between their cells. The plasma levels of soluble adhesion molecules increase in patients with ischemic heart disease, atherosclerotic aortic disease. Hypercholesterolemia is one of risk factors for atherosclerosis, and it is considered that the expression of adhesion molecules in endothelial cells is related to the development of atherosclerosis. Low-density lipoprotein (LDL) apheresis has been applied to patients with hypercholesterolemia. LDL apheresis may have an effect on adhesion molecules in patients with hypercholesterolemia.
Ther Apher Dial 2003 Aug
PMID:The effect of apheresis on adhesion molecules. 1288 26

C-reactive protein (CRP) is one of the important risk factors for atherosclerosis, and its serum level is lowered by popular cholesterol-lowering drugs, statins. This study was undertaken to examine the changes of CRP levels during dextran-sulfate (DS) low-density lipoprotein (LDL) apheresis. In 15 apheresis sessions in seven patients with severe hypercholesterolemia (four men and three women, aged between 36 and 70 years), changes in CRP levels were examined. The efficiency in adsorption of CRP with DS column was evaluated by measuring CRP levels in both pre- and post-column plasma. In one patient, the effect of repeated apheresis sessions on CRP preapheresis levels was examined. The changes in interleukin (IL)-6 plasma levels were also examined in six sessions. Although IL-6 levels after 3,000 mL-plasma treatment rose to 170% of preapheresis levels, CRP levels decreased significantly (from 1.91 +/- 0.49 mg/L to 0.89 +/- 0.24, P < 0.01). C-reactive protein was almost completely adsorbed by the DS column and CRP preapheresis levels were decreased gradually by repetition of apheresis. CRP, a novel risk factor of atherosclerosis, was effectively removed by DS-LDL apheresis. The decrease in CRP plasma levels may be involved in prevention of atherosclerotic vascular diseases due to DS-LDL apheresis.
Ther Apher Dial 2003 Aug
PMID:Changes in C-reactive protein plasma levels during low-density lipoprotein apheresis. 1288 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>