Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been proposed that hyperinsulinemia may not constitute a cardiovascular risk in women, and that the metabolic risk profile is less apparent in women than in men. In two different studies, we have assessed the interrelationship between classical coronary risk factors in women with untreated essential hypertension and looked for possible hypertensive-normotensive differences. Hypertensive women (HT1, 156 +/- 2/98 +/- 1 mm Hg, n = 18) in study I turned out to be overweight and had nearly three times higher fasting serum insulin levels than the normotensive control subjects (NT1, 118 +/- 3/77 +/- 2 mm Hg, n = 9). HT1 women with a body mass index (BMI) above 25 kg/m2 had significant higher insulin levels than HT1 women with a BMI less than 25 kg/m2, and when adjusting for BMI the hypertensive-normotensive difference in insulin levels was lost. In HT1 women, the serum insulin level correlated positively to the BMI and triglycerides. In study II, insulin was positively associated with the systolic blood pressure in HTII women (150 +/- 3/99 +/- 1 mm Hg, n = 29), and a negative correlation appeared between the glucose/insulin ratio and the systolic as well as diastolic blood pressure. No difference was observed in BMI and insulin between HTII and NTII women (121 +/- 3/79 +/- 1 mm Hg, n = 18). In HTII women, plasminogen activator inhibitor (PAI-1) levels were higher and the euglobulin clot lysis time prolonged compared to NTII women. PAI-1 was positively correlated to insulin and triglycerides and negatively to high-density lipoprotein (HDL) cholesterol in HTII women. Strong associations between potential cardiovascular risk factors seem to be present even in untreated women with mild hypertension, with insulin being correlated to hypertension, BMI, fibrinolytic activity, triglycerides, and HDL cholesterol.
 ...
PMID:Hypertension and the metabolic cardiovascular syndrome: special reference to premenopausal women. 128 64

Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. 186 24

Hypertension is related to several conditions with abnormalities in carbohydrate and lipid metabolism, such as obesity and impaired glucose tolerance. However, perturbed metabolism is also seen in non-obese hypertensive individuals. In addition, hypertension is linked to impaired fibrinolysis and elevated levels of the plasminogen activator inhibitor of endothelial type (PAI-1). Insulin resistance and hyperinsulinaemia in essential hypertension may be an important cause of these metabolic and fibrinolytic abnormalities. Whether hyperinsulinaemia is the cause of hypertension is currently unknown. However, it is clear that the relationship between hypertension and insulin is complex, and further studies are required to clarify this association. Based on the evidence states, it is suggested that insulin resistance and hyperinsulinaemia play a role in hypertension. However, it is also clear that hyperinsulinaemia occurs in the absence of hypertension, which suggests that other factors, such as genetic susceptibility, may be important.
 ...
PMID:Hypertension as a metabolic disorder--an overview. 204 18

Despite effective antihypertensive therapy, essential hypertension is still associated with considerable residual risk of cardiovascular complications. The aim of the present study was to investigate the state of the endogenous fibrinolytic system in young subjects with borderline hypertension. Thirty-nine young (age, 24 to 34 years) male subjects with borderline hypertension (systolic BP [SBP] 140 to 160 mm Hg and/or diastolic BP [DBP] 85 to 95 mm Hg) and 17 normotensive control subjects (age, 22 to 31 years; SBP 110 to 130 and DBP 60 to 80 mm Hg) were recruited from a population screening. Plasma levels of tissue-type plasminogen activator (t-PA) antigen and activity and plasminogen activator inhibitor 1 (PAI-1) antigen were determined at rest and in response to a venous occlusion test. Borderline-hypertensive subjects had metabolic and anthropometric characteristics similar to normotensive individuals. In comparison with normotensive subjects, borderline-hypertensive subjects had higher plasma concentration of t-PA antigen both at rest and after venous occlusion but similar levels of t-PA activity or PAI-1 antigen. The increase in t-PA antigen and activity in response to venous occlusion was significantly greater in borderline-hypertensive subjects than in normotensive control subjects (P < .0001 and P = .003, respectively). In stepwise regression analyses, 24-hour mean arterial pressure emerged as the single most powerful predictor of t-PA antigen levels, but body mass index was the most important determinant of t-PA activity and PAI-1 antigen. However, PAI-1 was explained by both body mass index (partial r = .48, P < .001) and 24-hour mean arterial pressure (partial r = .29, P < .05). Thus, early hypertension may be associated with significant alterations in endogenous fibrinolysis.
 ...
PMID:Enhanced levels of tissue-type plasminogen activator in borderline hypertension. 759 Oct 20

The incidence of atherosclerotic and thromboembolic complications is quite high in hypertensive patients. Blood platelets and fibrinolytic activity may play an important role in the development of these complications. We investigated fibrinolytic activity and in vivo platelet release reaction in essential hypertension. Plasma levels of beta thromboglobulin (BTG), platelet factor-4 (PF4), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and plasminogen were determined in 36 essential hypertensive and 20 age and sex-matched control subjects. Plasma BTG levels were significantly higher in the hypertensive subjects than in controls (p < 0.05), whereas PF4 levels were similar for both groups suggesting an increase of in vivo platelet activity. PAI-1 antigen levels were found to be significantly higher in the hypertensive patients as compared to the control subjects (p < 0.01). On the other hand significant variations of t-PA antigen and plasminogen values were not observed in the two groups. These results suggest that essential hypertension is associated with decreased fibrinolytic activity and enhanced platelet activity as evidenced by high plasma levels of PAI-1 and BTG.
 ...
PMID:Fibrinolytic activity and platelet release reaction in essential hypertension. 789 22

Insulin resistance has been implicated in the pathogenesis of essential hypertension. Studies from other countries discovered insulin resistance; in people with essential hypertension in was also associated with obesity, however, insulin resistance was found in lean people too. In obesity, insulin resistance occurs secondarily to many physiopathological states and circulating factors which adversely affects insulin action. The metabolic abnormality in this action was mainly found in relation to abdominal fat; in other cases, insulin resistance was found to be inherited. Hyperinsulinaemia can actually increase blood pressure and is associated with venous and arterial thrombosis and it also rises lipid levels. It is interesting too that insulin resistance and hyperinsulinaemia are associated with impaired fibrinolysis through high levels of fibrinogen and plasminogen activator inhibitor of endothelial type and in identifying individuals prone to myocardial infarction. Some antihypertensive drugs like beta-blockers, methyl-dopa and diuretics increase insulin resistance, while angiotensin converting enzyme-inhibitors have not shown any adverse metabolic affects. Alfa-1-blocker were beneficial and alfa-2-agonists were neutral, whereas calcium channel-antagonists are still in controversy. Treatment should be designed to improve the metabolic state; physical exercise, a diet rich in fruit, vegetable and rott vegetables, the reduction of abdominal fat and, finally, the use of antihypertensive drugs which decrease insulin resistance would be expected to reverse hyperinsulinaemia. Biguanides like metformin have also been found to reduce insulin resistance.
 ...
PMID:[Insulin resistance: an etiological factor in essential arterial hypertension and coronary cardiopathy]. 792 20

The insulin resistance syndrome has been noted as an interesting and important new risk factor for coronary artery disease. The syndrome consists of hypertension, glucose intolerance, and dyslipidemia, all of which are likely to be derived from insulin insensitivity. In subjects with nonobese and nondiabetic essential hypertension, steady-state plasma glucose (SSPG) was higher than in normotensive subjects during an insulin sensitivity test, indicating reduced insulin sensitivity to glucose metabolism in the hypertensive group. SSPG correlated with the percentage decrease of branched chain amino acids, free fatty acids, and serum potassium during the insulin sensitivity test. With a 2-h insulin infusion, serum norepinephrine, epinephrine, plasminogen activator inhibitor 1, and intraplatelet Ca2+ decreased significantly, but 6-keto-prostaglandin (PG) F1 alpha and PGE2 did not change. Insulin resistance decreased by using antihypertensive treatments with bunazosin, cilazapril, amlodipine, and benidipine in hypertensive subjects. Diagnostic criteria for the insulin resistance syndrome, including clinical values for each risk factor, were developed. Lowered insulin sensitivity and hyperinsulinemia were demonstrated in subjects with both vasospastic and coronary artery stenotic angina. The insulin resistance syndrome together with hyperinsulinemia is likely to induce atherosclerotic changes, possibly through reduced rather than excessive action of insulin.
 ...
PMID:Mechanism and clinical implication of insulin resistance syndrome. 867 91

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.
 ...
PMID:Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors. 884 3

This study assessed the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the main haemostatic variables in 22 patients, of either sex, with newly diagnosed uncomplicated essential hypertension. In the patients and in 10 control subjects, plasma levels of thrombomodulin, beta-thromboglobulin, D-dimer, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) had previously been measured. Only the levels of t-PA and PAI-1 were found to be higher than in controls. All these haemostatic evaluations were carried out after 6 and 12 months of treatment with an ACE inhibitor, cilazapril, 5 mg/day. This treatment significantly lowered the mean arterial pressure in the whole group from 133 to 106 mm Hg (after 6 months) and to 105 mm Hg (after 12 months), p < 0.05. No significant difference in any haemostatic parameters was observed after 6 and 12 months of treatment. The present study confirmed that treatment with cilazapril for 12 months lowers daytime ambulatory mean arterial pressure in patients with essential hypertension, without any significant increase in the tendency of blood to clot.
 ...
PMID:Effects of medium-term antihypertensive therapy on haemostatic parameters in patients with essential hypertension. 909 84

Vascular cell adhesion molecule-1 (VCAM-1) is a protein expressed on the surface of activated endothelial cells and expressed in early atherosclerosis. Because part of the protein is shed in the circulation and can be detected in peripheral plasma [soluble (s) VCAM-1], we hypothesized that sVCAM-1 may be a circulating marker of the presence and severity of atherosclerosis in humans. We selected 11 patients with essential hypertension plus peripheral vascular disease (PVD) and matched them for age, gender, body mass index, and smoking habits with 11 patients with uncomplicated essential hypertension (UH) and 11 healthy controls. We evaluated plasma concentrations of sVCAM-1 along with those of the soluble form of two other endothelial leukocyte adhesion molecules [sE-selectin and s-intercellular adhesion molecule-1 (sICAM-1)] and other markers of endothelial dysfunction/ damage [s-thrombomodulin, plasminogen activator inhibitor type I, and von Willebrand factor (vWF)]. We also measured insulin, glucose, fibrinogen, total and HDL cholesterol, and the urinary albumin excretion (UAE), which may also be related to atherosclerosis. Results of these assays were related to the echographic assessment of the maximum intima-media thickness (IMTmax) at the carotid bifurcation, as an index of atherosclerosis in the carotids. PVD patients had a clearly elevated IMTmax [2.7 (1.1-3.1) mm, median (range)] compared with both UH patients [1.2 (0.8-2.4) mm] and controls [1 (0.6-2) mm]. sVCAM-1 was clearly higher in PVD patients [990 (273-1808) ng/mL, median (range)] versus 340 (236-975) ng/mL in UH and 386 (204-835) ng/mL in controls, and it separated clinical categories better than sICAM-1, vWF, glucose, insulin, UAE, triglycerides, or total, LDL or HDL cholesterol, sVCAM-1 was also the best biohumoral correlate of IMTmax (R = .59; P < .001) in univariate analysis. Because many of the biohumoral variables assessed were mutually intercorrelated, they were entered in a multivariate analysis to assess their contribution in explaining IMTmax variability. sVCAM-1 remained the only independent predictor of IMTmax and totally abolished the contribution of other variables to IMTmax variability. Thus, sVCAM-1 is a good biohumoral correlate of overt atherosclerosis, independent of underlying hypertension, and may be an in vivo marker of endothelial activation. Its potential value as a surrogate for global risk assessment and its behavior in intervention studies remain to be determined.
 ...
PMID:Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis. 940 38


1 2 Next >>