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Query: UMLS:C0028754 (obesity)
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Hypertensive patients have an excess of other cardiovascular risk factors. Moreover, traditional therapy based on diuretics and beta-blockers may aggravate these risk factors. Therefore, attention must be given to the identification of all pertinent risk factors and their amelioration by appropriate therapy. Such therapy must include lifestyle changes including cessation of smoking, reduction of obesity, moderation of sodium intake and alcohol consumption, and increased physical activity. When antihypertensive drugs are chosen, consideration should be given to their potential influences, either negative or positive, on other cardiovascular risk factors. In particular, the adverse effects of diuretics and beta-blockers on lipids and insulin sensitivity may preclude their use. alpha-Blockers and ACE inhibitors may have beneficial effects on these metabolic indices. Calcium antagonists are neutral in most regards. Whatever agents are chosen, the use of low doses in combination is being increasingly recognized as a better way to achieve the desired antihypertensive efficacy while minimizing adverse effects. As has been noted in the other papers in this supplement, the combination of an ACE inhibitor and a calcium antagonist is particularly attractive, not only to treat hypertension, but also to ameliorate other cardiovascular risk factors.
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PMID:The challenge of managing multiple cardiovascular risk factors. 923 94

In subjects with coronary artery diseases (obstructive and vasospastic angina pectoris (AP)) who have no diabetes, hypertension, obesity and physical inactivity, insulin sensitivity was significantly reduced with compensated hyperinsulinemia on OGTT. Insulin resistance significantly correlated with coronary atherosclerosis score. In vasospastic AP (VAP), those who fulfilled more than 3 risk factors out of 5 (hyperinsulinemia, obesity, glucose intolerance, hypertension, dyslipidemia) consist of 70 and 40% for smokers and nonsmokers respectively. Insulin resistance syndrome who fulfilled all the criteria was 9-10% for VAP. In atherothrombotic brain infarction (ATTI) with the same exclusion criteria, the similar insulin resistance and hyperinsulinemia have been observed, but not in embolic (cardiac origin) or lacunar infarction. In ATTI, high TG and apo B with low HDL-chol were noted in blood. In essential hypertension without diabetes and obesity, hyperinsulinemia was noted in 25-35% and insulin resistance in 56-88%. Reduction of blood pressure with alpha blocker (bunazosin), ACE inhibitor (cilazapril), long-acting Ca++ blocker (amlodipine) significantly improved lowered insulin sensitivity. Insulin resistance rather than hyperinsulinemia is more closely associated with blood pressure. Cardiovascular diseases (vasospastic and obstructive AP, brain cortical artery diseases) are prone to develop diabetes because of insulin resistance and also promote the generation of cumulative risk factors resulting in a vicious cycle. Efforts to alleviate insulin resistance is crucial for the primary and secondary prevention of cardiovascular diseases.
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PMID:Clinical impact of insulin resistance syndrome in cardiovascular diseases and its therapeutic approach. 924 Jul 71

There has been increasing interest in the question of whether microalbuminuria can be used in the risk stratification of patients with essential hypertension. A cluster of cardiovascular and/or renal risk factors may be associated with microalbuminuria in hypertension. Despite this, prospective data about the potential role of microalbuminuria as a prognostic marker of cardiovascular and/or renal risk have been sparse and inconclusive until now. Blood pressure values have been considered the most important determinant of microalbuminuria in essential hypertension; however, hyperinsulinaemia--a metabolic component-was noted to be present in conjunction with high blood pressure. Furthermore, 2 other factors may be also related to microalbuminuria: salt sensitivity and renal structural changes (nephrosclerosis). We are now aware that the clinical and physiological implications of abnormal urinary albumin excretion (UAE) are much broader than anticipated, possibly involving haemodynamic, metabolic and vascular components overlapping several clinical syndromes. Achievement of short term UAE reduction with antihypertensive treatment depends on structural abnormalities established in the glomerulus, the extent of blood pressure reduction and the antihypertensive drug class used. In terms of UAE reduction, better results are obtained with ACE inhibitors or angiotensin II antagonists such as losartan and valsartan, than with other antihypertensive classes, although their true impact in preserving renal function needs to be assessed. The capacity of new calcium antagonists, such as amlodipine, lacidipine or mibefradil, to reduce UAE also needs to be assessed further. Thus, microalbuminuria may be seen as an integrated marker of risk and should be assessed in recently diagnosed patients with essential hypertension. In microalbuminuric patients, the target should be to decrease blood pressure < 135/85 mm Hg, reduce salt intake to around 100 mmol/day and prescribe a low-calorie diet if obesity is present. ACE inhibitors or angiotensin II antagonists have more potential benefits than the other classes of antihypertensive drugs in reducing UAE. Finally, a yearly assessment of microalbuminuria is recommended during treatment, to monitor the impact of therapy.
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PMID:Treatment of patients with essential hypertension and microalbuminuria. 942 93

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

Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
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PMID:[Insulin resistance. Receptor and post-receptor abnormalities]. 984 54

In the C57BL/6J mice model, we investigated whether obesity affects the function or expression of components of the tissue renin-angiotensin system and whether endothelin (ET)-1 contributes to these changes. ACE activity (nmol. L His-Leu. mg protein(-1)) was measured in lung, kidney, and liver in control (receiving standard chow) and obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone or in combination with LU135252, an orally active ET(A) receptor antagonist. ACE mRNA expression was measured in the kidney, and the effects of LU135252 on purified human ACE were determined. Aortic and renal tissue ET-1 protein content was measured, and the vascular contractility to angiotensin II was assessed. Obesity was associated with a tissue-specific increase in ACE activity in the kidney (55+/-4 versus 33+/-3 nmol/L) but not in the lung (34+/-2 versus 32+/-2 nmol/L). Long-term LU135252 treatment completely prevented this activation (13.3+/-0.3 versus 55+/-4 nmol/L, P<0.05) independent of ACE mRNA expression, body weight, or renal ET-1 protein but did not affect pulmonary or hepatic ACE activity. Obesity potentiated contractions in response to angiotensin II in the aorta (from 6+/-2% to 33+/-5% KCl) but not in the carotid artery (4+/-1% to 3.6+/-1% KCl), an effect that was completely prevented with LU135252 treatment (6+/-0.4% versus 33+/-5% KCl). No effect of LU135252 on purified ACE was observed. Thus, obesity is associated with the activation of renal ACE in vivo independent of its mRNA expression and enhanced vascular contractility to angiotensin II. These effects are regulated by ET in an organ-specific manner, providing novel mechanisms by which ET antagonists may exert organ protection.
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PMID:Obesity is associated with tissue-specific activation of renal angiotensin-converting enzyme in vivo: evidence for a regulatory role of endothelin. 1064 20

Hypertension is currently defined in terms of levels of blood pressure associated with increased cardiovascular risk. A cut-off of 140/90 mm Hg is accepted as a threshold level above which treatment should at least be considered. This would give a prevalence of hypertension of about 20% of the adult population in most developed countries. Hypertension is associated with increased risk of stroke, myocardial infarction, atrial fibrillation, heart failure, peripheral vascular disease and renal impairment. Hypertension results from the complex interaction of genetic factors and environmental influences. Many of the genetic factors remain to be discovered, but environmental influences such as salt intake, diet and alcohol form the basis of nonpharmacological methods of blood pressure reduction. Investigation of the individual hypertensive patient aims to identify possible secondary causes of hypertension and also to assess the individual's overall cardiovascular risk, which determines the need for prompt and aggressive therapy. Cardiovascular risk can be determined from (i) target organ damage to the eyes, heart and kidneys; (ii) other medical conditions associated with increased risk; and (iii) lifestyle factors such as obesity and smoking. Secondary causes of hypertension are individually rare. Screening tests should be initially simple, with more expensive and invasive tests reserved for those in whom a secondary cause is suspected or who have atypical features to their presentation. The main determinants of blood pressure are cardiac output and peripheral resistance. The typical haemodynamic finding in patients with established hypertension is of normal cardiac output and increased peripheral resistance. Treatment of hypertension should initially use nonpharmacological methods. Selection of initial drug therapy should be based upon the strength of evidence for reduction of cardiovascular mortality in controlled clinical trials, and should also take into account coexisting medical conditions that favour or limit the usefulness of any given drug. Given this approach, it would be reasonable to use a thiazide diuretic and/or a beta-blocker as first-line therapy unless there are indications to the contrary. Individual response to given drug classes is highly variable and is related to the underlying variability in the abnormal pathophysiology. There are data to suggest that the renin-angiotensin system is more important in young patients. The targeting of this system in patients under the age of 50 years with a beta-blocker (or ACE inhibitor), and the use of a thiazide diuretic (or calcium antagonist) in patients over 50 years, may enable blood pressure to be controlled more quickly.
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PMID:Pathoaetiology, epidemiology and diagnosis of hypertension. 1067 92

Some 44% of all patients with elevated blood pressure are overweight. In obesity-related hypertension, sympathicotonia is regularly found, together with elevated intracellular calcium, sodium retention, increased cardiac output (per minute) and a sensitivity to salt. The role played by hyperinsulinemia has apparently been overstated. A primary rise in the minimal vascular resistance suffices to reduce the perfusion of the skeletal musculature and, solely on this basis, to induce insulin resistance. For the treatment of obesity-related hypertension, non-medicinal approaches to weight reduction predominate. Reducing the daily salt intake to 5 g can also bring about a measurable reduction in blood pressure. For the treatment with antihypertensive drugs, beta blockers and diuretics are the initial choice; in the case of pronounced metabolic syndrome, ACE-inhibitors and alpha-1 receptors.
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PMID:[Fat control--an effective antihypertensive strategy. Special recommendations for therapy of the overweight patient]. 1079 42

This study aimed at analysing an effect of the coronary risk factors and pharmacotherapy on the long-term outcome in women following the coronary artery by-pass. In 1004-1997, 253 female patients, aged between 33 and 82 years (mean [+/- SD] 57.0 +/- 8 years) were treated surgically. The follow-up period lasted for 7 to 60 months (mean 32.0 +/- 14 months). Ten patients (3.9%) died. Answers to the questionnaire and personal interviews assessed physical fitness based on CCS classification, pharmacotherapy, and presence of risk factors. According to CCS scale, significant improvement has been seen in 195 (82.6%; p < .0001) patients. Health state did not change in 34 (14.4%) patients, and deteriorated in 7 (3.0%). Analysisn coronary risk factors, hypertension proved prevailing (60.3%), followed by diabetes mellitus (25.5%) and obesity (22.9%). Eleven percent of patients returned to cigarettes smoking after surgery. Postoperatively, 74.1% of patients received nitrates as a constant, medication, 58.2%--beta-blockers, 53.4%--ACE inhibitors, and 19.8% of patients received calcium antagonists. Lipid abnormalities have been treated in 49.1% of patients whereas antiplatelet therapy has been carried out in 74.1%. Only 9.9% of patients received hormones. The lower CCS class before surgery, the more significant improvement after it. As pharmacotherapy was used according to the European guidelines, an improvement in the long-term outcome required some modifications in patients' life style.
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PMID:[An influence of cardiovascular risk factors and pharmacotherapy on the long-term results in women undergoing coronary artery bypass]. 1080 40

More women than men eventually develop hypertension in the United States due to their higher numbers and longer longevity. The white coat hypertension is also more common in women. Alcohol, obesity and oral contraceptives are important causes of rise in blood pressure among women. On the other hand, hormone replacement therapy may decrease cardiovascular mortality in the postmenopausal woman. Women with left ventricular hypertrophy are at a greater risk of death than men. Fibromuscular hyperplasia and primary aldosteronism are more common as causes of secondary hypertension in women. Nonpharmacologic therapy, such as weight reduction, exercise, salt and alcohol reduction, should always be tried prior to medical treatment of hypertension and are very useful adjunctive measures in controlling hypertension. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy and should be avoided in women with childbearing potential. Hypertension remains a major public health problem among black women. Although the antihypertensive drug therapy seems to benefit white women the least, proportionately more of them comply with their antihypertensive therapy. Hypertension is the most common chronic medical condition requiring visits to the physicians, as well as prescription medications, in the United States. The epidemiology, clinical course, response to treatment and ultimate outcome of essential hypertension may vary with gender. More women than men eventually develop hypertension in the US due to their higher numbers and longer longevity.
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PMID:Hypertension in women. 1092 86


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