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

Most people with diabetes die from thrombotic complications superimposed to degenerative arterial vascular lesions, mostly myocardial infarction. Diabetes is a risk factor per se for such complications, but often clusters with dyslipoproteinemia, hypertension and obesity. In NIDDM (Type-II) patients this is referred to as "metabolic syndrome" and often operates on a genetically programmed susceptibility which accelerates the pathogenesis of coronary artery disease in front of a much wider diabetes specific cardiopathy. From a pathophysiological point of view none of these associated risk factors explains the pathogenetic series of events leading to the precipitation of an occlusive thrombus at sites of complicated coronary plaques. In patients with diabetes the coagulation system is switched towards a prethrombotic state, involving increased plasmatic coagulation, diminished fibrinolysis, decreased endothelial thromboresistance and predominantly platelet hyperreactivity ("diabetic thrombocytopathy"). Some of these factors are associated with an increased coronary risk (e.g. fibrinogen, PAI-1, platelets), but are also directly linked to the pathogenesis of "atherothrombosis". Altered cardiac remodelling together with adhesion and coagulation mechanisms appears suitable to explain decreased functional performance of infarcted organs, decreased success of acute (reduced fibrinolytic response, reperfusion injury) and longterm intervention strategies (PTCA, CABG) in diabetes. Glucose adjustment alone will not adequately neutralize these complex mechanisms. Particularly in diabetes a multidimensional interventional repertoire is required including antihypertensive, antidyslipoproteinemic and antithrombotic drugs, customized according to the individual patients needs as assessed by early diagnostic measures ("early secondary prevention").
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PMID:Heart disease in diabetes mellitus: a challenge for early diagnosis and intervention. 951 54

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
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PMID:Management of dyslipidemia in adults with diabetes. 953 88

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.
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PMID:Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. 954 28

Thromboembolic complications such as ischemic stroke and myocardial infarction are significantly more frequent in patients with arterial hypertension. From the available intervention studies, it appears that pharmacologic treatment of hypertension-at least with diuretics and beta-blockers-may more effectively protect against cerebrovascular as compared to coronary thromboembolic events. Whether other antihypertensive substances provide a more effective protection with respect to cardiac morbidity and mortality is the subject of numerous studies presently underway. These studies will help to answer the question of whether the extent of protection from coronary events during antihypertensive treatment depends on factors beyond blood pressure control. The fibrinolytic system is crucially involved in the pathogenesis of thromboembolic events. One determinant of this system is the balance between plasminogen activators (tissue-type plasminogen activator [t-PA]) and inhibitors (plasminogen activator inhibitor 1 [PAI-1]). Experimental and clinical evidence suggests that at least some of the drugs used in the treatment of hypertension may alter the activity of the fibrinolytic system. Scarce and controversial data with respect to such an interaction exist with respect to diuretics, beta-blockers, and calcium antagonists. In addition, experimental evidence demonstrates that PAI-1 is stimulated by angiotensin II (A II), whereas t-PA is activated by bradykinin. Thus, antihypertensive drugs acting within the renin angiotensin system should exert effects also within the fibrinolytic system. However, results from clinical studies with angiotensin converting enzyme (ACE) inhibitors and A II receptor antagonists do not unequivocally support such a concept. The discrepancy in the results may, at least in part, be explained by studies performed in healthy volunteer subjects showing that ACE inhibition profoundly affected fibrinolysis only during stimulation of the renin angiotensin system by NaCL restriction.
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PMID:Antihypertensive drug treatment and fibrinolytic function. 979 46

In health, the vascular endothelium forms a multifunctional interface between the circulating blood and various tissues and organs of the body. It constitutes a selectively permeable barrier for macromolecules, as well as a nonthrombogenic and nonadhesive container that actively maintains the fluidity of blood. It is a metabolically active endocrine organ, serving as the source of multiple factors and mediators that are critical for normal homeostasis. These include vasodilators (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor), vasoconstrictors (endothelin-1, thromboxane A2, prostaglandin H2 and components of the renin angiotensin system), various pro- and antithrombotic factors (e.g. tissue factor, platelet activating factor--PAF, von Willebrand factor), fibrinolytic activators and inhibitors (e.g. tissue plasminogen activator, plasminogen activator inhibitor-1), potent arachidonate metabolites (prostanoids), leukocyte adhesion molecules (e.g. E-selectin, P-selectin, intercellular adhesion molecule-1--ICAM-1, vascular cell adhesion molecule-1--VCAM-1), and multiple cytokines with activities of growth stimulators and inhibitors, transforming growth factors, proinflammatory and antiinflammatory mediators, tumour necrosis factors and chemotactic factors (chemokines). Besides these essential activities controlling the cardiovascular system, the endothelial cells represent an important part of the immune system as well. They have a pivotal role in the initiation and development of defensive and damaging inflammatory responses. Therefore endothelium can be considered as being the central equipment for the mutual exchange of life important information between the cardiovascular and immune systems. This in turn is leading to rapid advances in understanding the pathogenesis of some of the most serious and most common diseases, including inflammation, atherosclerosis and hypertension. (Tab. 7, Ref. 89.)
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PMID:[Vascular endothelium as a factor in information transfer between the cardiovascular and immune systems]. 958 73

In Caucasian subjects, an insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with coronary artery disease (CAD) and fatal myocardial infarction. The underlying mechanism(s) of this association is not fully understood. Pima Indians have a low incidence of nonfatal and fatal CAD despite a high prevalence of diabetes. In Pima Indians, circulating ACE levels are related to ACE genotype, but the frequency of the D allele is significantly lower than in Caucasians. A lower frequency of the D allele may underlie a low risk of CAD in this population. We examined the relationship of the ACE genotype and plasma ACE level with electrocardiographic evidence of CAD (Tecumseh criteria), hypertension, and metabolic variables associated with insulin resistance in 305 (146 men and 159 women aged 47+/-9.0 years) Pima Indians characterized for the ACE I/D genotype. The distribution of ACE genotypes was unrelated to diabetes and obesity. Fasting plasma insulin, plasminogen activator inhibitor-1 (PAI-1) activity, plasma triglyceride concentrations, and systolic (SBP) and diastolic (DBP) blood pressure were not significantly different between the three ACE genotypes among nondiabetic and diabetic subjects. There was no significant association of ACE genotype with electrocardiographic evidence of CAD or with hypertension. Plasma ACE concentrations were not significantly different between nondiabetic and diabetic subjects (median, 77 [range, 21 to 1691 v 83 [7 to 238] IU/mL, P=NS). In all subjects, plasma ACE levels were associated weakly with plasma triglyceride (partial r=.20, P < .01) and total cholesterol (partial r=.13, P <.03) concentrations, but not with fasting plasma insulin or PAI-1 activity. In diabetic subjects, ACE levels were related to fasting plasma glucose concentrations (partial r=.15, P=.07). These findings would suggest that ACE gene I/D polymorphism is unlikely to be a major determinant of susceptibility to CAD in Pima Indians. Plasma ACE levels, but not ACE genotype, correlated with lipids, plasma glucose, and blood pressure, suggesting that elevated plasma ACE levels may contribute to the link between insulin resistance and CAD disease or may be a consequence of it.
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PMID:Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians. 959 57

The alpha-blockers prazosin and doxazosin reduce hypertriglyceridemia (HTG) and increase serum levels of high-density lipoprotein (HDL)-cholesterol, whereas beta-blockers such as atenolol have the opposite effect. As HTG is associated with reduced fibrinolysis and hypercoagulability, we investigated the effects of doxazosin and atenolol on serum lipids and hemostatic factors in hypertensive men with an atherothrombogenic risk profile. The study was randomized and open, but blinded to investigator of biochemical results. Forty-five men (mean age, 44.5 years) with central obesity [median body-mass index (BMI), 28 kg/m2] and moderate hypertension [median diastolic blood pressure (DBP), 104.5 mm Hg] were treated with atenolol (n = 22) or doxazosin (n = 23) for 22 weeks, after which changes in between-group differences from baseline were estimated. After intervention, significant between-group differences in favor of doxazosin were found: lower triglycerides (p = 0.008) and higher HDL cholesterol (p = 0.036); furthermore, improvement of fibrinolysis: lower plasminogen activator inhibitor-1 (PAI-1) activity (p = 0.012), higher tissue plasminogen activator (tPA) activity after venous occlusion (VO); and higher levels of serum D-dimer, both unstimulated (p = 0.0016) and after VO (p = 0.0032). In addition, lower levels of serum testosterone were found in the atenolol group (p = 0.0016). A profile with reduced HTG, increased HDL cholesterol, and improved fibrinolysis was obtained with doxazosin when compared with atenolol. Furthermore, the observed decrease in serum testosterone on atenolol treatment would rather favor long-term treatment with doxazosin in this study population.
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PMID:Effects of doxazosin and atenolol on atherothrombogenic risk profile in hypertensive middle-aged men. 959 66

The high atherogenic potential of the insulin resistance syndrome can be only partly explained by the association of "classical" risk factors of atherosclerosis which are considered part of it, i.e. impaired carbohydrate tolerance/diabetes mellitus type II, dyslipidaemia, hypertension and obesity. Impaired fibrinolysis due to excessive production of the plasminogen activator inhibitor-1 (PAI-1) are further risk factors which participate in the process of atherogenesis from the beginning of formation of the atheromatous plaque to the thrombotic occlusion of the vascular lumen. The authors present a group of 25 patients with different grades of glucose resistance, evaluated by theinsulin response to a glucose load. The insulin resistant group (n = 15) differed significantly from the non-resistant one (n = 10) as regards body weight and the central type of obesity (< 0.01 and 0.001 resp.) insulin level on fasting and after a load (< 0.0001 and 0.001 resp.), triglyceride levels (< 0.01), the incidence of diabetes or impaired carbohydrate tolerance (66.7 vs. 20%) and hypertension (53.3 vs. 20%), but also as regards the PAI-1 activity (.0001). As regards blood sugar levels, total and HDL cholesterol the groups did not differ. The authors investigated also the relationship between PAI-1 activity and different components of the insulin resistance syndrome in the whole group. The closest correlation was found between the PAI-1 activity and the general insulinaemic response to a glucose load (< 0.001) and between PAI-1 and triglycerides (< 0.001). Based on the presented results it may be stated that hypofibnrinolysis as a result of excessive production of PAI.1 is part of the insulin resistance syndrome and potentiates its high atherogenic risk.
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PMID:[The insulin resistance syndrome and fibrinolysis disorders]. 960 68

To investigate how cigarette smoking increases the risk of cardiovascular disease, risk factors were compared between 166 cigarette smokers and 312 non-smokers, in a random sample of males (Chinese, Malays and Asian Indians) aged 30-69 years from the general population of Singapore. There was adjusted for age and ethnic group. The prevalence of hypertension was lower in cigarette smokers (15.2%) than non-smokers (21.9%), with the difference reduced by adjustment for body mass index (BMI). Smokers had: lower mean serum HDL-cholesterol (0.76 versus 0.81 mmol/l) and higher mean serum fasting triglyceride (1.92 versus 1.71 mmol/l), which will increase atherosclerosis; higher mean plasma fibrinogen (2.75 versus 2.67 g/l) and plasminogen activator inhibitor 1 [PAI-1] (24.9 versus 22.2 ng/ml), which will increase thrombosis; and lower mean plasma vitamin C (4.4 versus 6.4 mg/l) and serum selenium (118 versus 123 microg/l), which may increase atherosclerosis. Adjustment for BMI slightly increased the differences for HDL-cholesterol, fasting triglyceride, fibrinogen and PAI-1, indicating that less generalised obesity among smokers reduces their increased cardiovascular disease risk. Smoking was not found to be related to: diabetes mellitus; serum total cholesterol, LDL-cholesterol, apolipoproteins A1 and B and lipoprotein(a); plasma factor VIIc and prothrombin fragment 1 + 2; and plasma vitamins A and E and serum ferritin. There was no evidence of increased insulin resistance in smokers, as measured by mean fasting serum insulin.
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PMID:Cardiovascular risk factors in relation to cigarette smoking: a population-based survey among Asians in Singapore. 962 68


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