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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetes mellitus are at increased risk of morbidity and mortality from macrovascular disease manifesting as coronary heart disease, cerebrovascular accidents, and peripheral vascular disease. Increased frequency of dyslipidemia, hyperglycemia, obesity, hypertension, and associated nephropathy may contribute to accelerated atherogenesis in diabetic patients. Therefore, besides intensive control of hyperglycemia, management of dyslipidemia, hypertension, and obesity should also be emphasized in diabetic patients. Those who smoke should be strongly encouraged to quit smoking. Besides attempts to achieve normal levels of plasma lipoproteins, consideration also should be given to normalization of compositional abnormalities of various lipoproteins in patients with diabetes mellitus. The therapeutic goals for cholesterol reduction should be lower in diabetic patients than nondiabetic subjects. The first step is to achieve good metabolic control of diabetes mellitus by diet, exercise, and weight reduction and, if needed, with sulfonylureas or insulin therapy. Because most of the patients with insulin-dependent diabetes mellitus achieve normal levels of plasma lipoproteins with intensive insulin therapy, lipid-lowering medications are rarely needed. In patients with non-insulin-dependent diabetes mellitus, however, dyslipidemia often persists despite good glycemic control. Lipid-lowering medications should be considered in such patients. Because nicotinic acid can cause marked deterioration in glycemic control, and bile acid-binding resins may accentuate hypertriglyceridemia, these agents are less desirable for use by diabetic patients. Inhibitors of hydroxymethylglutaryl coenzyme A reductase may be preferred in patients with elevated LDL cholesterol and mld hypertriglyceridemia. For diabetic patients with marked hypertriglyceridemia, however, fibric acid derivatives should be the drug of choice.
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PMID:Lipid-lowering therapy and macrovascular disease in diabetes mellitus. 152 29

For the past 40 years, adrenoreceptors have been studied as the biomolecular mediators of tissue response to catecholamines. An expanded role of alpha-adrenoreceptors in the regulation of risk factors for coronary heart disease (CHD) has recently emerged. Hypercholesterolaemia, hypertension, and cigarette smoking are the major risk factors and their interactions are associated with increased mortality. Control of hypertension alone has failed to reduce the risk of CHD. Conversely, reduction of elevated total cholesterol and low density lipoprotein (LDL)-cholesterol has been shown to lower the risk of CHD. As a result, multiple risk factor approaches to the management of patients have evolved in attempts to reduce deaths from CHD. Selective alpha 1-adrenoreceptor antagonists appear to have a dual function in CHD risk management since they control elevated blood pressure by peripheral vasodilatation and reduce atherogenic lipids by several mechanisms. With selective alpha 1-blockade, the number of LDL-cholesterol receptors is up-regulated and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG Co-A reductase) activity is suppressed causing reductions in total cholesterol, LDL-cholesterol, and apoprotein B levels. Effects on intermediary metabolism reduce synthesis of very low density lipoprotein (VLDL) which contributes to a reduction of total triglyceride levels and, to a lesser extent, to a reduction of total cholesterol levels. Increased lipoprotein lipase activity leads to reduced total triglyceride and VLDL levels and to increased high density lipoprotein (HDL)-cholesterol levels. As demonstrated by the initial prospective data from Phase I of the Treatment of Mild Hypertension Study (TOMHS), both reduction of raised blood pressure and beneficial lipid modifications are sustained (1 year) with selective alpha 1-blockade. The prospective benefits on morbidity and mortality from CHD of such favourable changes in these two major risk factors remain to be quantified.
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PMID:Alpha 1-adrenoreceptor blockade and the molecular basis of lipid metabolism alterations. 197 19

This review will concentrate on more recent evidence on the prevention of coronary heart disease and hypertension. With the evidence from lipid-lowering regimes using cholestyramine or gemfibrozil, it is clear that cardiovascular mortality can be reduced by relatively short interventions (years rather than decades). This is surprising in a disease with a long incubation period. We are also on the threshold of much more powerful intervention with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Follow-up of the very large number of subjects screened for the Multiple Risk Factor Intervention Trial study showed that the relation between serum cholesterol and risk is linear, with no hint of a "safe" level or threshold. This is borne out with the data from rural Chinese, who show the same trend, albeit at levels of risk that are 4% of those of Western populations. The suggestion that low cholesterol levels increase cancer risk appears to result from an artifact. The best dietary interventions for cholesterol lowering are still unresolved, with recent interest in fish oil and olive oil. On the background of raised cholesterol (most Western levels could be regarded as biologically abnormal), cigarette smoking assumes very great importance. Recent evidence from the U.S. Nurses survey points out a two- or threefold increase in risk from as few as four cigarettes per day. With other risk factors the relative risk increases 20-fold. These data are particularly important given that young girls in the United Kingdom and United States currently smoke more than boys.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of coronary heart disease and hypertension. 246 24

Hypertensive patients who smoke have a high risk of developing premature cardiovascular disease. In addition to encouraging these patients to stop smoking, effective nondrug therapies include weight reduction, salt restriction, and alcohol limitation. For patients whose hypertension is severe or who have other health problems, antihypertensive drug therapy is also used. In the past, diuretics and beta-blockers have proved popular. However, these drugs have produced biochemical disturbances, such as diuretic-induced hypokalemia and both diuretic- and beta-blocker-induced alterations in blood lipids. The hazard of such drug-induced alterations may be greater in hypertensive patients, who may already suffer from hypercholesterolemia. Other drugs are available that can treat hypertension with no or beneficial influence on blood lipids. For smokers, the selective alpha 1-receptor inhibitors may be more attractive, since they also act to counteract the vasoconstriction produced by nicotine. In the future, inhibitors of hydroxymethylglutaryl coenzyme A reductase may offer potential for effective control of blood lipids in hypertensive patients who smoke.
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PMID:Strategies to reduce risk factors in hypertensive patients who smoke. 333 96

We undertook this cross-sectional study to compare the mechanical behavior and postischemic response of the radial artery of 15 newly diagnosed hypercholesterolemic patients with those of 15 age- and sex-matched normocholesterolemic control subjects and 21 hypercholesterolemic patients treated for 2 years with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (simvastatin, 10 to 20 mg/d). At the time of the study total cholesterol levels were at 7.9 +/- 0.2, 4.9 +/- 0.2, and 6.0 +/- 0.3 mmol/L in the three groups, respectively (mean +/- SEM, P < .001). High-resolution, noninvasive echotracking for assessment of internal arterial diameter was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. Radial cross-sectional compliance and distensibility were similar in all groups. Forearm blood flow and flow-mediated dilation were measured after a 5-minute upper arm occlusion. Flow was calculated from the vessel diameter and blood flow velocity recorded simultaneously at the same site. Flow-mediated dilation after ischemia was not significantly different among the three groups. However, forearm blood flow increase was markedly blunted (P < .01) in untreated hypercholesterolemic patients (211%) compared with the normocholesterolemic control subjects (411%) and treated patients (365%). These findings suggest that the distensibility of the radial artery, a muscular conduit vessel usually devoid of atherosclerotic lesions, and its flow-mediated dilation are preserved in hypercholesterolemic patients. In contrast, forearm resistance vessels exhibit a markedly reduced postischemic blood flow response that may be restored by prolonged lipid-lowering intervention.
Hypertension 1995 Sep
PMID:Postischemic blood flow response in hypercholesterolemic patients. 764 88

Patients with diabetes mellitus have an increased risk for coronary artery disease due to hyperglycemia, hypertension, dyslipidemia, and other risk factors. The diabetic dyslipidemia in these patients is characterized by moderately high levels of (1) serum cholesterol and triglycerides; (2) small, dense low-density lipoprotein (LDL) particles; and (3) low high-density lipoprotein (HDL) cho-lesterol concentrations. Recent clinical trials have demonstrated the benefits of cholesterol-lowering therapy in both diabetic and nondiabetic patients, thus supporting aggressive treatment of diabetic dyslipidemia for coronary artery disease prevention. A 3-step approach is recommended for the treatment of diabetic dyslipidemia. First, modification of diet and lifestyle, including decreased intakes of cholesterol, cholesterol-raising fats, and total energy, and increased physical activity should be advised. Second, good glycemic control should be achieved with diet and hypoglycemic drugs, if needed. Third, lipid-lowering drugs should be used, if necessary. Non-HDL cholesterol levels, which include both very-low-density lipoprotein (VLDL) and LDL cholesterol, should be the target of cholesterol-lowering therapy. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (the "statins") has become the first-line drug therapy for diabetic dyslipidemia. Bile acid sequestrants are effective cholesterol-lowering agents in normotriglyceridemic patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients with severe hypertriglyceridemia may require fibric acids or n-3 polyunsaturated fatty acids. Nicotinic acid worsens hyperglycemia; therefore, it should be avoided in most cases. The efficacy and safety of estrogen-replacement therapy in postmenopausal women with diabetes needs to be determined. The combination of two lipid-lowering agents may be appropriate for some NIDDM patients but should be used judiciously.
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PMID:Treatment of diabetic dyslipidemia. 952 14

Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29+/-0.52 mmol/L, systolic and diastolic blood pressure 149+/-6 and 97+/-2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins.
Hypertension 1999 Dec
PMID:Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia. 1098 83

An increasing body of evidence suggests that an endogenous mammalian bufadienolide (BD) may be involved in the regulation of Na(+),K(+)-ATPase activity and the pathogenesis of arterial hypertension. We developed a purification scheme for marinobufagenin (MBG), an amphibian cardiotonic BD, and applied it to purify and characterize material in human plasma, culture medium conditioned by Y-1 adrenocortical cells, and rat adrenal tissue. MBG immunoreactivity purified from plasma and measured by ELISA showed important similarities (chromatography and antibody cross-reactivity) to material secreted into cell culture medium by Y-1 cells. This observation indicates that circulating mammalian BD may have an adrenocortical origin. Release of mammalian BD from adrenocortical cells grown in the absence of exogenous cholesterol was reduced by treatment of cultures with mevastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Supplementation of the serum and cholesterol-free cell culture medium with the LDL fraction of human plasma increased the production of MBG material in the presence of mevastatin, supporting its origin from cholesterol. We used Y-1 cell lines transfected with genes shown to inhibit steroidogenesis through cholesterol side-chain cleavage (Y-1/DAX and Y-1/RIAB) to investigate the dependence of MBG biosynthesis on side-chain cleavage. Our results indicate that the mammalian BD is synthesized in the adrenal cortex from cholesterol and shares important similarities with the amphibian BD MBG, that its biosynthesis is independent of transfer of cholesterol to the side-chain cleavage enzyme complex mediated by steroidogenic acute regulatory protein, and that neither cAMP nor protein kinase A appears to be a critical component of the pathway controlling its biosynthesis.
Hypertension 2000 Sep
PMID:Mammalian bufadienolide is synthesized from cholesterol in the adrenal cortex by a pathway that Is independent of cholesterol side-chain cleavage. 1098 79

Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal insufficiency (CRI). beta-Adrenergic blockers, acetylsalicylic acid (ASA), angiotensin-converting enzyme (ACE) inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) all reduce CVD mortality, but little is known about the extent to which these medications are used in patients with CRI. This study, a prospective cross-sectional study of consecutive patients seen by nephrologists in four Canadian centers for follow-up of progressive CRI in 1999, was performed to investigate the prevalence of coronary risk factors and use of cardioprotective medications among patients with CRI. Patients had creatinine clearances of 75 mL/min or less but were not on dialysis therapy. Three hundred four consecutive patients meeting the inclusion criteria were enrolled. Mean age was 60.8 +/- 15.7 years, mean creatinine clearance was 30.3 +/- 18 mL/min, and the case mix of kidney diseases was similar to that in the Canadian Organ Replacement Registry data. One hundred seventeen of 304 patients (38.5%) had a history of previous CVD, and the prevalence of CVD was greater in patients with more severe CRI. Two hundred forty-three patients (79.9%) had a history of hypertension, 132 patients (43.4%) had hyperlipidemia, 114 patients (37.5%) had diabetes mellitus, and 71 patients (27.3%) were smokers. Thirty-five percent of the patients with CVD had blood pressures greater than 140/90 mm Hg; 103 patients (33.9%) were administered beta-blockers; 196 patients (64.5%), ACE inhibitors or angiotensin-receptor blockers; 83 patients (27.3%), ASA; and 56 patients (18.4%), statins. Patients with diabetes were not more likely than those without diabetes to be prescribed cardioprotective medications. CVD is common in the predialysis population, and its prevalence increases with more severe kidney failure. Despite this, the use of cardioprotective medications is relatively low, and many patients had suboptimal blood pressure control. Given the high burden of disease in these patients, beta-blockers and ACE inhibitors should be used to control hypertension and/or for cardioprotection, and the increased use of ASA and statins should be considered.
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PMID:Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency. 1122 71

Clinical trials continue to guide patient management. However, the hypotheses generally come from observational studies. Studies on women continue to be too little and too few, particularly in light of the fact that most elderly hypertensive patients are likely to be women. Attention has been drawn to the possibility that hypertension per se may engender symptoms such as headache for example, in addition to harder endpoints such as death. The MICROHOPE study, which was not a blood pressure-lowering study, showed that angiotensin converting enzyme inhibition with ramipril in diabetic patients provided the same beneficial effects previously published for the HOPE study. The doxazosin arm of the ALLHAT study was terminated by the data monitoring and safety board because the doxazosin-treated patients developed congestive heart failure at a greater rate than diuretic-treated patients. Two extensive studies testing two different classes of calcium antagonists against primarily diuretic-based treatment showed that the calcium antagonists were no less effective in terms of preventing hard endpoints. A small, but impressive cross-over study testing the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, against placebo showed that statin treatment lowers blood pressure in hypercholesterolemic patients with hypertension. Meta- analyses emphasized the value of blood pressure reduction in the elderly and added to the controversy and confusion about the role of calcium antagonists in the first-line treatment of hypertension. The point may be moot since with the current recommendations few hypertensive patients will be adequately treated with a single agent.
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PMID:Recent clinical trial highlights in hypertension. 1127 95


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