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)

The endothelium is increasingly recognized as a modulator of vascular tone, and evidence also is accumulating for an important role of the endothelium in humans in vivo. Endothelial release of prostacylin appears to regulate hyperemic blood flow after ischemia and muscle exercise, and the potent vasodilating properties of endothelium-derived relaxing factor (EDRF) are well established. Tonic release of EDRF plays an important role in the regulation of vascular tone in normal subjects, and a reduction of EDRF release in response to muscarinergic stimulation has been described in subjects with uncomplicated hypertension and also in hyperlipidemic patients. These observations point toward an early disturbance of endothelial function in disorders known as risk factors for the development of atherosclerosis. Furthermore, altered EDRF release and responsiveness to stimuli may be involved in the disturbed regulation of peripheral vascular tone in congestive heart failure. The physiological role of the vasoconstricting peptide endothelin-1 is not yet defined, but the study of the vascular actions of the peptide in humans has shown a vasodilating effect (for low dosages or when the vasconstricting effects are blocked), as well as a marked and long-lasting vasoconstricting effect. Although the mechanisms leading to vasodilation are not clear in humans, endothelin-1-induced vasoconstriction appears to be completely dependent on the activity of voltage-operated calcium channels and can be blocked by organic calcium antagonists but not by nitrovasodilators or EDRF. Further clarification of the role of the endothelium will provide a better understanding of circulatory physiology and pathophysiology and eventually may lead to the development of new therapeutic modalities.
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PMID:Endothelial function in humans. Studies of forearm resistance vessels. 191 1

Careful consideration of all relevant scientific evidence and a critical assessment of data quality show that thiazide diuretics are not cardiotoxic. Of 12 reported trials only two recorded more coronary heart disease events in thiazide-treated patients than in controls. One of these two was a subgroup of a larger study (Heart Attack Prevention in Primary Hypertension, HAPPHY) which found no difference between thiazide-treated and beta-blocker-treated patients. The other, the Oslo study, was too small to allow valid conclusions. Results from a subgroup in the Multiple Risk Factor Intervention Trial (MRFIT) that appeared to supply evidence for thiazide-related cardiotoxicity are suspect when examined critically. Further evidence from 24- to 28-h ECG monitoring does not support the hypothesis that thiazide diuretics, either in the presence or absence of hypokalemia, increase the frequency or severity of ventricular arrhythmias. Reports of a thiazide-induced intracellular magnesium deficiency as a cause of ventricular arrhythmias have also not been confirmed; the development of arrhythmias in acute myocardial infarction appears to be due to an increase in catecholamine levels rather than hypokalemia. There appears to be little evidence to support the assumption that long-term use of thiazide diuretics aggravates or accelerates atherosclerosis of the coronary arteries; any fall in serum cholesterol appears to be transient. For the great majority of patients with uncomplicated hypertension, without a previous myocardial infarction, congestive heart failure, diabetes mellitus or gout, thiazide diuretics appear to be both safe and effective antihypertensive agents.
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PMID:The cardiotoxicity of thiazide diuretics: review of the evidence. 221 84

Therapy of essential hypertension (HT) should not imply the simple lowering of blood pressure alone but also reduction of the trophic effects provoked on the vascular system. Regression of left ventricular hypertrophy must be combined with "remodelling" of the overall arterial network to adapt to the abnormal physical forces acting on the vascular wall. This adaptive process has both qualitative and functional effects with structural modifications of the large arterial trunks as well as the smaller arteries, provoking adverse effects once they increase vascular resistance and diminish large artery compliance. Additionally, they tend to induce chronicity of HT, particularly since at the crossroad of these pathologic processes exist anomalies of endothelial secretory function. Treatment of HT should therefore comprise care of the vascular system, inasmuch as common mechanisms of cellular hypertrophy and proliferation are found in uncomplicated hypertension and atherosclerosis.
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PMID:[Arterial hypertension, vascular remodelling and atherosclerosis]. 847 16

Despite its important role in coronary disease, coronary atherosclerosis has been poorly investigated in uncomplicated hypertension. Therefore, we evaluated the presence and amount (score) of coronary calcium with ultrafast computed tomography in 73 pairs of age-matched asymptomatic hypertensive or normotensive men. We also estimated the extent of peripheral atherosclerosis as the number of arterial sites (carotid, aortic, femoral) with echographic plaque. Compared with normotensive men, hypertensive men had more frequent coronary calcium (63% versus 47%), a higher calcium score (57 +/- 111 versus 18 +/- 38), and an odds ratio of calcium deposit of 1.95 (with confidence intervals [CI] 95%, 1.01 to 3.79) for any score and of 2.38 (95% CI, 1.02 to 5.52) or 4.84 (95% CI, 1.53 to 15.3) for scores above 50 or 100, respectively. Hypertensive men showed correlations of calcium score with age and hypertension duration but not with the height of blood pressure, and the odds ratio of calcium deposit between extensive and minor peripheral atherosclerosis was 4.67 (95% CI, 1.41 to 15.45) for any score and 8.63 (95% CI, 2.10 to 35.5) or 8.13 (95% CI, 1.64 to 40.3) for scores above 50 or 100. Thus, high blood pressure and in particular its duration rather than its value promotes the presence and overall extent of coronary calcium, a potential predictor of sudden coronary death, in parallel with the extent of peripheral atherosclerosis. The mechanisms of the interaction of hypertension and coronary calcification may be multifactorial and not specific to hypertension.
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PMID:Hypertension promotes coronary calcium deposit in asymptomatic men. 861 73

1. Increased urinary albumin excretion is common in patients with essential hypertension and is at least to some extent correlated with prevailing blood pressure levels. However, the generalized vascular dysfunction present in advanced atherosclerotic disease may independently influence this parameter. 2. To evaluate this possibility, we assessed blood pressure, ultrasonographic carotid thickness, cardiac mass, minimum forearm vascular resistances, metabolic parameters and the angiotensin-converting enzyme genotype in patients with untreated essential hypertension and atherosclerotic peripheral vascular disease (n = 11). The results were compared with similar data obtained in matched groups of patients with uncomplicated hypertension and with normotensive control subjects (n = 11 per group). 3. Urinary albumin excretion was higher in hypertensive patients with atherosclerosis than in those without complications; carotid thickness was higher in atherosclerotic patients and a positive, statistically significant correlation existed between this parameter and urinary albumin excretion. In the same patient group, systolic blood pressure, fasting insulin and triacylglycerol levels were elevated and correlated with urinary albumin levels. However, differences in urinary albumin excretion persisted after taking into account the influence of those parameters by analysis of covariance. The distribution of angiotensin-converting enzyme genotype patterns and values of cardiac mass and minimum forearm vascular resistances did not differ significantly among the experimental groups. 4. The data suggest that vascular status may influence urinary albumin excretion in patients with essential hypertension, while confirming the importance of systolic blood pressure levels as a determinant of the raised urinary albumin excretion.
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PMID:Urinary albumin excretion and atherosclerosis in essential hypertension. 903 90

The aim of the present analysis was to calculate the cost-effectiveness of metoprolol versus thiazide diuretics in middle-aged men with mild to moderate uncomplicated hypertension. The analysis was based on the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) study, a randomised trial which showed a significantly lower risk for coronary events in patients taking metoprolol than in patients on thiazide diuretics. The main analysis was based on Swedish costs, but the costs were also varied in a special sensitivity analysis. Metoprolol was shown to be cost-saving compared with thiazide diuretics when both direct and indirect costs of morbidity were included. When only direct costs were included, the cost per life-year gained was $US2400. The result of the present analysis suggests that metoprolol is to be preferred to thiazide diuretics from a cost-effectiveness standpoint in the treatment of mild to moderate hypertension in middle-aged men. These findings regarding cost-effectiveness should, however, not be extrapolated to patient groups not included in the MAPHY trial.
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PMID:Cost-effectiveness of antihypertensive treatment: metoprolol versus thiazide diuretics. 1014 86

It is well-known that patients with terminal renal insufficiency are at increased risk for a future cardiovascular event. A relevant relationship also appears to apply to the early stages of renal insufficiency. The HOPE study has shown that the incidence of myocardial infarction, apoplexy and cardiovascular mortality in patients with incipient renal insufficiency is significantly raised. The study also found that the incidence of cardiovascular events is in direct proportion to the level of serum creatinine. Against this background, patients at risk can be readily identified. The HOPE study documents a considerable cardiovascular risk for patients with incipient renal insufficiency and concomitant uncomplicated hypertension, atherosclerosis or diabetes. In view of this, the use of ACE inhibitors in patients with moderate renal insufficiency should now be introduced. In the HOPE subjects, ramipril was found not only to lower the cardiovascular risk, but also to improve renal insufficiency.
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PMID:[Renal failure and cardiovascular risk. Increased borderline serum creatinine--a warning sign?]. 1177 Mar 72

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.
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PMID:Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. 1214 57

Uric acid (UA) is the final product of purine catabolism in man, and it is excreted mainly by the kidneys when renal function is not impaired. Consequently, serum (S) UA increases as a function of purine intake, and it varies inversely to uricosuria. The latter variable diminishes in response to low-sodium intakes and vice versa. Insofar as the diet is not usually controlled in studies in which the response of SUA to drugs is evaluated, most reports are to be considered cautiously. Common diuretics elevate SUA in healthy subjects, hypertensives and patients with heart failure, apparently by elevating net UA reabsorption in the nephronal proximal tubule. This drug action, which becomes noticeable shortly after the institution of treatment and remains throughout it, starts at low doses (e.g., 12.5 mg hydrochlorothiazide or 1.25 mg bendrofluazide once daily in subjects with uncomplicated hypertension) and increases in dose-dependent fashion. Beta-blockers tend to elevate SUA. The angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril and ramipril have been found to increase uricosuria mildly, likely by lowering the net reabsorption of UA in the proximal tubule. These three drugs and lisinopril can blunt the rise in SUA provoked by diuretics in hypertensives if used at sufficiently high doses relative to the dose of the diuretic. The angiotensin II antagonist losartan augments uricosuria mildly and thereby decreases SUA. The cardiovascular implications of the response of SUA to drugs remain speculative. Uric acid can scavenge various reactive oxygen species and thus reduce oxidative stress, which seems to contribute to the development and/or progress of various cardiovascular conditions, including hypertension, atherosclerosis and heart failure. Consequently, it may be theorised that the elevations in SUA induced by diuretics might contribute to the established favourable action of these agents on cardiovascular prognosis. Conversely, diuretic-induced increases in SUA are to be considered detrimental according to an old hypothesis that maintains that SUA is a cardiovascular risk factor; this construct is largely based upon the results of selected epidemiological undertakings. The cardiovascular implications of the effects of drugs on SUA, if any, should be elucidated through purposive research.
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PMID:Cardiovascular drugs and serum uric acid. 1510 95

Limited evidence is available about the relationship between ambulatory heart rate (HR) and target organ damage (TOD) in uncomplicated hypertension. We sought to investigate the association between ambulatory HR and subclinical cardiac, vascular and renal markers of TOD in never-treated essential hypertensives. A total of 580 subjects with recently diagnosed (<or= 1 year) grade 1 and 2 hypertension, categorized by tertiles of HR levels, assessed by two 24-h ambulatory blood pressure monitoring at 1- to 4-week interval, sex and the presence or absence of TOD were considered for this analysis. All subjects also underwent laboratory and ultrasonographic investigations searching for microalbuminuria (MA), left ventricular hypertrophy (LVH) and carotid atherosclerosis (carotid thickening/plaque). In the whole population, as well as in both genders, LVH, carotid atherosclerosis and MA prevalence rates did not significantly increase with 48-h HR tertiles. When patients were categorized according to the presence or absence of TOD (that is, LVH, carotid atherosclerosis or MA) no significant intergroup differences in 48-h HR were found. Furthermore, average 48-h HR was similar in patients without organ involvement as in those with one, two or three TOD signs. Finally, in a multivariate analysis age, 48-h systolic blood pressure and metabolic syndrome assessed by ATP III criteria, but not HR were independently associated with TOD. Our findings showing that 48-h ambulatory HR is not associated with markers of TOD do not support the view that a faster HR may have an additive value in predicting organ damage in the early phases of essential hypertension.
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PMID:Ambulatory heart rate and target organ damage in never-treated essential hypertensives. 1782 95


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