Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aging is accompanied by a progressive and irreversible non-enzymatic modification of protein by carbohydrates, eventually yielding the advanced glycation end products (AGEs). Age generation (Maillard reaction) is markedly augmented in diabetes with sustained hyperglycemia but also in normoglycemic uremia and atherosclerosis. Recent studies have brought new insights into broad derangements in non-enzymatic biochemistry involving not only carbohydrates but also lipids, present in diabetes, uremia, and atherosclerosis. The latter have in common increased levels of reactive carbonyl compounds (RCOs) with attendant protein modifications ("carbonyl stress"). Carbonyl stress might be derived from 1) hyperglycemia (lipemia), 2) oxidative stress, and/or 3) impaired detoxification of RCOs. Manipulation of carbonyl stress in diabetes, uremia and atherosclerosis opens new therapeutic approaches including redox modulation, RCO detoxification, and carbonyl stress inhibition. The first generation of carbonyl stress inhibitors such as aminoguanidine trap RCOs with its hydrazine group. Unfortunately, aminoguanidine (AG) traps pyridoxal as well as noxious RCOs, so that its long-term administration in animals results in vitamin B6 deficiency and neurotoxicity. Fortunately, newer compounds devoid of such side effects, have opened exciting prospects. Widely used hypotensive agents, such as angiotensin converting enzyme (ACE) inhibitor and angiotensin II receptor antagonist, but not calcium blockers, prove more effective than AG in attenuating the production of AGEs. Unlike AG, they do not act as RCO trapping agents, but impact upon the production of RCO precursors by scavenging a variety of radicals and altering oxidative stress, a mechanism similar to that involved in the inhibitory action of nitric oxide on AGE formation. These results provide a new framework to assess families of compounds according to their mechanisms of action.
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PMID:Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis ("carbonyl stress"). 1250 15

Steroid Resistant-Nephrotic Syndrome (NS) is a chronic, progressive disorder affecting upto 10% of all children with NS. It causes morbidity and mortality due to persistent edema, hypertension, hyperlipidemia, thrombosis and infection. Progression to renal failure was thought to be inevitable in survivors. Recent insights into the pathogenesis of the disease has identified several responsible genes and proteins. Studies have shown that long term aggressive therapy with combinations of steroids, alkylating agents and cyclosporine, cause complete or partial remission in 20-80% patients. The use of nonspecific renal protective agents such as the angiotensin converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid agents retard disease progression. Although these are indications of significant improvement in outcome, further multicentre controlled studies are required to determine the optimum drugs and regimens to be used.
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PMID:Steroid resistant nephrotic syndrome. 1255 61

Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the 'response to injury' paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloantigen-independent factors include donor-transmitted coronary artery disease, surgical trauma, ischaemia-reperfusion injury, viral infections, hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic advances include the use of novel immunosuppressive agents such as sirolimus (rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular risk factors remains of paramount importance.
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PMID:Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy. 1283 11

With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest cause of mortality in diabetic patients. The concept that type 2 diabetes and CVD are linked via a common etiologic pathway (metabolic syndrome) has substantial ramifications for the care of individual patients. Many of the metabolic abnormalities that contribute to both glycemic disorders and CVD are interrelated. For example, hyperinsulinemia and insulin resistance coupled with abdominal obesity further worsens HTN and hyperlipidemia. Likewise, the procoagulant state and endothelial dysfunction increase with worsening glycemic control. Specific interventions include tobacco cessation, a food management and physical activity plan, choice of antidiabetic agent (such as metformin), and use of ACE inhibitors for hypertension and microalbuminuria (Table 5). Programs to enhance cardiovascular risk factor reduction as part of the comprehensive evaluation and management of diabetic patients have been described [95,99]. One community-based program provided free screening to diabetic patients with randomization to either annotated result reports provided to the patient and their physician or results provided by a project nurse (either face-to-face or over the phone). Greater improvements in mean glycohemoglobin, cholesterol, and blood pressure were noted with verbal presentation of results [99]. Recent data from the Centers for Disease Control and Prevention Diabetes Cost-effectiveness Group support the idea that interventions to decrease CVD in diabetics are economically beneficial. Intensive management of hypertension, glycemic control, and hyperlipidemia each improved health outcomes. Hypertension control reduced costs. Although intensive treatment of glucose and hyperlipidemia increased costs, the increase was comparable to that of other frequently used health care interventions [100]. Further directions include further exploration of the implications and management of metabolic syndrome as it relates to CVD prevention. Interventions such as exercise, which can impact on all outcomes, require special attention. Efforts by physicians, health systems, and society are necessary to increase physical activity for individuals of all ages. It makes clinical sense that the recommendations for prevention of CVD in diabetics described in this article may also benefit patients with prediabetes (fasting glucose 110-125 mg/dl), but this remains to be definitively shown.
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PMID:Preventing cardiovascular disease in diabetes and glucose intolerance: evidence and implications for care. 1469 2

Systemic embolism is a frequent cause of stroke. At the beginning of the last decade by introduction of transesophageal echocardiography and other imaging techniques atheromatosis of the aortic arch has been recognized as an important source of embolism. Formerly in the pre-TEE era, this entity was included into cryptogenic strokes. Aortic atheromas are found in about one quarter of patients presenting with embolic events. The severity of atherosclerosis graded by TEE correlates with the risk for future embolism, especially if mobile lesions or superimposed thrombi are present. Independent of plaque extension, patients with unstable plaques characterized by echo-lucency, inhomogenity, lacking of calcifications, ulceration, mobile parts and concomitant spontaneous echo contrast within the aorta have a higher risk for embolic events. However, the diagnosis of aortic atheromatosis is mostly established if an embolic event has already occurred. Therefore, it is important to identify patients at risk, especially before they undergo interventions with manipulation at the aorta like coronary bypass surgery. Risk factors are age above 70, diabetes mellitus, hyperlipidemia, arterial hypertension, aortic calcifications on standard chest X-ray, elevated serum levels of C-reactive protein, other inflammatory markers, and an activated coagulation. Randomized studies for treatment of patients with severe aortic atheromatosis are not yet existing. Warfarin has been shown to prevent stroke in patients with mobile atheromas and superimposed thrombi, but there are case reports about aggravation of cholesterol embolism under warfarin treatment. It is concluded from other atherosclerotic manifestations that plaque stabilizing treatment with statins and ACE inhibitors is also beneficial.
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PMID:Atheromatous disease of the thoracic aorta and systemic embolism. Clinical picture and therapeutic challenge. 1474 Feb 36

In the last decade the number of patients with congestive heart failure has increased noticeably and today heart failure is one of the major problems in civilized countries. While in earlier decades arterial hypertension was the main reason for developing heart failure, today coronary artery disease has become the focus of attention. However, arterial hypertension, diabetes and hyperlipidemia are also main risk factors for developing coronary artery disease. In addition to non-pharmacological management with reduced fluid intake and periodical exercise training particularly in stable heart failure, in the last decade some special drug compounds have demonstrated a significant reduction in mortality in great double blind randomized trials. ACE-inhibitors and betablockers are essential components in treating congestive heart failure. Angiotensin-II-receptorblockers are indicated if ACE inhibitors and/or beta-blockers are not tolerated. The combined use of all three compounds was shown to result in a further reduction of mortality in the recently presented CHARM study. In progressive heart failure the use of diuretics is necessary and effective especially when fluid overload exists. Not treating heart failure is followed by high mortality, as we know, and so adequate and uncompromising treatment of hypertension is the most important approach to prevent the further development of heart failure.
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PMID:[Therapeutical strategies in hypertensive patients presenting heart failure symptoms]. 1500 83

Around one third of patients with myocardial infarction are diabetic. More vigorous control of hyperglycemia, hyperlipidemia, and hypertension is likely to be of crucial importance for risk reduction. Although the effect of intensive glycemic control appears to be only minor in terms of prevention of cardiac events in diabetic patients, it has a major beneficial impact during acute myocardial infarction and after percutaneous transluminal coronary angioplasty. Lipid-lowering treatment is as effective in diabetic patients with coronary artery disease as in nondiabetic patients. In patients with coronary artery disease, there is strong evidence in favor of the use of b-blockers soon after myocardial infarction as well as in the long term. The metabolic treatment may also be considered as a rational approach for patients with stable angina. The long-term angiotensin converting enzyme inhibitor trials in patients with left ventricle dysfunction soon after myocardial infarction demonstrated a substantial benefit in the subgroup of diabetic patients. Current evidence leads us to recommend revascularization surgery as the first choice in diabetic patients. The management of risk factors should be more intensive in diabetic patients. In diabetic patients with coronary artery disease, most of the medical strategies are as effective as in nondiabetic patients.
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PMID:[Treatment of patients with ischemic heart disease and diabetes]. 1500 79

Several intervention studies have shown that some hypolipidemic and hypotensive drugs such as fibrates, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, angiotensin converting enzyme (ACE) inhibitors and calcium (Ca)-antagonists prevent atherosclerosis. The main pathological findings in atherosclerosis include abnormal reactions of neutrophils, lymphocytes and monocytes/ macrophages, vascular smooth muscle cells and vascular endothelial cells, and the accumulation of cholesterol ester in the arterial wall. Therefore, investigating the effects of these drugs on the arterial wall may improve understanding of the mechanisms underlying atherosclerosis. Here, based on recent studies including our own, we describe the relationships between risk factors for atherosclerosis, especially hyperlipidemia and hypertension, and the molecular mechanisms that govern lipid metabolism in the arteries.
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PMID:The possible therapeutic actions of peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists, PPAR gamma agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, angiotensin converting enzyme (ACE) inhibitors and calcium (Ca)-antagonists on vascular endothelial cells. 1503 51

About 60% of patients with mild and moderate hypertension have insulin resistance and half of them have clinically manifest metabolic syndrome which comprises abdominal obesity, hyperlipidemia, impaired glucose tolerance, hypertension and insulin resistance. In a framework of metabolic syndrome hypertension is characterized by disturbed circadian profile without nocturnal blood pressure lowering and concentric left ventricular hypertrophy. There exist 2 mechanisms of linkage between hypertension and metabolic syndrome: impaired ion transport and neurohormonal and humoral activation. Antihypertensive drugs for correction of hypertension in metabolic syndrome should be long acting, provide protection of target organs, and induce positive or neutral metabolic effect. Together with normalization of blood pressure these actions can cause lowering of risk of atherosclerosis development. Representatives of the following classes of antihypertensive agents can be used as drugs of choice: angiotensin converting enzyme inhibitors, long-acting calcium antagonists, selective beta1-adrenoblockers, and thiazide diuretics.
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PMID:[Arterial hypertension in a framework of metabolic syndrome: special features and principles of drug correction]. 1511 79

The prevalence of ischemic heart disease (IHD) has been increasing among the women in developed countries. The well recognized IHD excess in men has often obscured the fact that IHD is the leading cause of death in women. Women have atypical symptoms of IHD that lead to a delay in the diagnosis and an overall poor prognosis. Women have a delay in the onset of IHD due to the beneficial effects of their sex hormones. Postmenopausal women lose this beneficial effect of estrogen and undergo significant changes in their lipid profile, arterial pressure, glucose tolerance, and vascular reactivity that increase their risk for development of IHD. Recently there has been considerable interest in the sex hormones and their role in IHD in women. The general belief that hormone replacement therapy (HRT) has an overall beneficial effect on cardiovascular disease (CVD) in women and hence decreases CVD mortality and morbidity has not been shown in the recent multicenter prospective studies. With the availability of various types of estrogen and progestins, physicians prescribing these agents should take into consideration their varying effects on the cardiovascular system. Risk factor modifications should include diet, weight loss, regular exercise, smoking cessation and adequate control of hypertension (HTN), diabetes (DM) and hyperlipidemia. In the appropriate setting, treatment with proven beneficial agents like aspirin, beta-blockers, angiotensin converting enzyme (ACE) inhibitors and statins will help decrease the burden of IHD in women.
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PMID:Ischemic heart disease in women and the role of hormone therapy. 1520 55


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