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

Individuals with abnormal glucose and insulin metabolism have a higher incidence of hypertension, and recent interest has focused on the fact that patients with untreated essential hypertension have higher than normal plasma insulin concentrations, are resistant to insulin-stimulated glucose uptake and often have accompanying lipid disorders. The pathophysiological significance of these observations lies in the findings that insulin has mitogenic properties and can potentiate vascular smooth muscle growth, thus promoting structural changes in vessels and atherosclerosis. Insulin could also promote high blood pressure via its effect in increasing sodium reabsorption and sympathetic nervous system activity. A variety of therapies is available for treatment of hypertension in patients with metabolic complications. Lifestyle modification is considered to be the initial approach, with weight management the most important component. Although diuretics and beta-blockers have a proven record in reducing morbidity and mortality, they may have adverse effects on glucose, insulin and lipids and should be used with caution in hypertensive subjects with metabolic risks. alpha-adrenergic blockers have favorable effects on lipids and glucose. Calcium antagonists have no adverse effect on glucose or insulin in patients with essential hypertension or diabetic patients with hypertension. ACE inhibitors, on the other hand, have neutral or beneficial effects on glucose, insulin and lipid metabolism, improving insulin sensitivity, insulin secretion, potassium balance and intermediary metabolism. Finally, oral hypoglycemic agents, which improve glucose metabolism and insulin sensitivity, can reduce blood pressure in obese, hypertensive subjects.
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PMID:Glucose and insulin metabolism in hypertension. 873 82

The issue as to whether antihypertensive drugs may exert some antiatherosclerotic effect, at least partly independent of blood pressure lowering, has been explored in several experimental models of atherosclerosis, and a large body of evidence has been obtained in favor of a specific antiatherosclerotic action of calcium antagonists and ACE-inhibitors. On the clinical side, several studies are investigating the problem in hypertensive patients in whom progression of carotid intima-media thickness (IMT) and atherosclerotic plaques is explored by sensitive quantitative B-mode ultrasound techniques. The MIDAS has indicated a slower progression, at least in the first six months, of carotid plaques in isradipine treated patients than in diuretic-treated ones. However, MIDAS as a pioneer study has been particularly valuable in giving information on the rate of growth of IMT in hypertensive patients and on the best end-point to use in carotid ultrasound trials. Baseline data of the ongoing studies ELSA and VHAS have so far provided evidence of the very high prevalence of carotid atherosclerosis among hypertensive patients, an observation that makes the evaluation of the antiatherosclerotic action of some antihypertensive agents even more important. Finally, the PHYLLIS trial using a factorial design, beside exploring the antiatherosclerotic action of an ACE-inhibitor vs a diuretic, intends to evaluate the possible benefits of associating antihypertensive therapy with lipid lowering by a statin on the progression of carotid atherosclerosis.
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PMID:Antiatherosclerotic effects of antihypertensive drugs: recent evidence and ongoing trials. 874 37

Hypertension should be detected and treated early in diabetic patients. It has a marked contribution to the morbidity and mortality of diabetic individuals due to both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. Prospective studies addressing the effects of antihypertensive regimens on the incidence of CHF, stroke, and coronary artery disease in the diabetic population are not available. We assume that the beneficial effects of therapy apply to both diabetic and nondiabetic subjects. Glycemic control and the lipid profile are major concerns when selecting an antihypertensive drug. Because hyperinsulinemia and insulin resistance have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may also become an important element in the selection of an antihypertensive agent. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer the most favorable metabolic profile when compared with diuretics and beta-blockers and should be used as the initial drugs in most clinical settings.
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PMID:Hypertension in diabetes mellitus. 879 6

Calcium antagonists are well accepted in the prevention of ischaemia in patients with chronic stable angina, unstable angina, variant angina, and silent ischaemia, and in the treatment of hypertension. Although all of these compounds increase myocardial oxygen supply by reducing coronary tone and decrease myocardial oxygen demand by reducing systolic pressure and myocardial contractility, the magnitude of these effects may differ from one agent to another. Some calcium antagonists, such as verapamil and diltiazem, reduce heart rate and attenuate heart rate increases in response to stress, while in contrast, dihydropyridine calcium antagonists such as nifedipine may cause reflex increases in heart rate. These differences may be of importance in light of epidemiologic evidence that lower heart rates are associated with a reduced long-term risk of cardiovascular mortality, and experimental data showing that a lower heart rate may protect against the development of atherosclerosis. Calcium antagonists also inhibit platelet aggregation and thrombus formation which may contribute to their anti-ischaemic effects. Clinical trial data suggest that calcium antagonists may stay the progression of atherosclerosis. Mechanisms underlying an anti-atherosclerotic effect may include attenuation of endothelial dysfunction, prevention of LDL, peroxidation, stimulation of LDL receptor activity, inhibition of superoxide radical generation, and inhibition of vascular smooth muscle cell growth. Heart-rate-controlling calcium antagonists, such as verapamil and diltiazem, may reduce reinfarction rates following acute myocardial infarction and thus may have a role in post-infarction patients who do not show evidence of heart failure. Their use in heart failure patients receiving an angiotension-converting enzyme inhibitor (ACE-I) is under investigation in several large trials. Because calcium antagonists have a mechanism of action different from ACE-I, the pairing of a heart-rate-controlling calcium antagonist with an ACE-I might be expected to offer additive cardioprotective and vascular protective effects.
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PMID:The role of calcium antagonists in ischaemic heart disease. 884 1

The activation of the renin-angiotensin system has been proposed as a very important step in the pathogenesis of atherosclerosis. Accordingly, ACE-inhibitors and angiotensin II receptors antagonists showed their ability to reduce the atherosclerotic process in animals. Inhibition of renin-angiotensin system reduces the development of atherosclerotic lesion either in cholesterol-fed animals and in animals after vascular injury. The precise mechanism for this action may depend on the inhibition of other than hypertensive property of angiotensin II.
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PMID:[Anti-atherosclerotic action of ACE inhibitors. I. Inactivation of the renin-angiotensin system]. 884 24

Dyslipoproteinemia in non-insulin-dependent diabetes mellitus (NIDDM) is an important risk factor in the development of atherosclerosis and glomerulosclerosis. The lipid profile of NIDDM patients is characterized by elevated serum triglycerides and VLDL levels and reduced HDL cholesterol levels. Serum LDL levels may be elevated as well in some patients with NIDDM, but several alterations in the biochemical and physical properties of LDL particles are more characteristic resulting in reduced receptor specific uptake of these lipoproteins. Non-enzymatic glycosylation of LDL and augmented oxidation is common in diabetic patients making lipoproteins susceptible for uptake by the macrophage scavenger receptors and thus leading to foam cell formation and further glomerular damage. A reduction in the progression of diabetic nephropathy by lowering proteinuria and thereby serum cholesterol during treatment with ACE-inhibitors demonstrates the importance of such a therapy. The multiple factors involved in the pathogenesis of diabetic nephropathy are difficult to evaluate in regard to their individual contribution. Nevertheless antiproteinuric and lipid lowering therapy can be expected to reduce vascular damage and the progression of diabetic nephropathy.
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PMID:Potential role of lipids in the progression of diabetic nephropathy. 890 13

Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected CAD [156 patients with a previous myocardial infarction (MI), 307 without MI]. Four angiographic scores assessing the extent and severity of the coronary lesions were obtained from a double visual analysis of each angiogram, arbitration being achieved by a quantitative measurement. Three different genotypes were analyzed: the angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the A to C transition at position 1166 of the angiotensin II type-1 receptor gene (AT1R A1166C). No significant association was observed between these polymorphisms and the clinical characteristics of MI and non-MI subjects. While most classical risk factors were positively correlated with the angiographic scores, no significant relationship could be established with the three genotypes (r ranging from -0.08 to 0.05). Only one significant correlation was observed: between the presence of the AGT 235T allele and the extent of the coronary lesions (r = -0.19, P = 0.04) in patients with low-risk status. These overall results are not in favor of a role of these RAS genetic polymorphisms in the development of coronary atherosclerosis.
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PMID:Genetic polymorphisms of the renin-angiotensin system and angiographic extent and severity of coronary artery disease: the CORGENE study. 900 97

Losartan potassium is the first of a new class of orally active antihypertensive drugs which antagonise the action of angiotensin (AT) II at the AT1 receptor subtype. Losartan potassium is converted by the liver to the active metabolite E-3174, which is a more potent antagonist at the AT1 receptor. E-3174 is responsible for most of the pharmacological effects of losartan potassium, and its long half-life contributes to the extended duration of action of the drug. Losartan potassium is effective as a once-daily antihypertensive agent. In mild to moderate hypertension, losartan potassium has similar efficacy to enalapril, atenolol and felodipine extended release. When losartan potassium is combined with hydrochlorothiazide there is a further reduction in blood pressure. Losartan potassium is well tolerated in mild, moderate and severe essential hypertension, with dizziness being reported as the only drug-related adverse effect. The overall rate of patient withdrawal from therapy due to adverse experiences with losartan potassium is lower (2.3%) than that of placebo (3.7%). First-dose hypotension is uncommon, perhaps due to the slower onset of action of the drug, and cough does not appear to be a significant problem. A number of areas concerning the safety and efficacy of losartan potassium remain to be clarified. In particular, long term tolerability studies are needed; cough only became apparent as an adverse effect of ACE inhibitors after 3 to 4 years of use. Postmarketing surveillance has shown that angioedema, a rare but life-threatening adverse effect of ACE inhibitors, also occurs with losartan potassium. Further data are needed on the use of losartan potassium in patients with renal impairment before accepting the recommendation that dosage adjustment is not necessary. The pharmacokinetics and pharmacodynamics of losartan potassium in patients with hepatic disease also require further investigation. Losartan potassium increases uric acid secretion and lowers plasma uric acid levels, which may be of benefit when losartan potassium is combined with a thiazide diuretic, but which may otherwise lead to uric acid stone formation and possibly to nephropathy. Simple control of blood pressure is no longer an adequate goal in the management of hypertension. Any new antihypertensive agent should also reduce cardiovascular events, prevent or cause regression of end-organ damage such as left ventricular hypertrophy, atherosclerosis and renal failure, and should not impair quality of life. Such data on losartan potassium are not currently available. Losartan potassium is likely to be used in patients who are intolerant of ACE inhibitors, but its future in the management of hypertension will depend on long term tolerability studies and data on its effects beyond simple blood pressure control.
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PMID:A risk-benefit assessment of losartan potassium in the treatment of hypertension. 901 Jun 43

The essential problem of the vicious circle leading to end-stage cardiovascular disease is atherosclerosis. This paper focuses on the functional changes centred on the endothelium that accompany the development of atherosclerosis, examining in particular pathological alterations in the L-arginine/nitric oxide (NO) pathway. Changes in the NO system are associated with altered platelet and monocyte interactions with the vessel wall, abnormal vasoconstriction and altered vascular structure. Diabetes, hyperglycaemia, hypertension and hypercholesterolaemia are all involved in this process. Endothelin is a vasoconstrictor peptide produced by endothelial cells which is upregulated under these conditions. Normalising endothelial function could involve platelet inhibition, lipid-lowering agents to prevent foam cell formation and decrease the lipid load of the blood vessel wall, and agents to interfere with some of the mechanisms involved in vasoconstriction, proliferation and migration, including ACE-inhibitors and angiotensin receptor antagonists, and possibly new tools such as endothelin receptor antagonists.
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PMID:The internist and the vessel wall. 917 1

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine > or = 2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develop cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists-ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.
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PMID:ACE inhibitors in heart failure: prospects and limitations. 921 Oct 22


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