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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A short review of the metabolic cardiovascular risk syndrome (MCVS) is given. Traditionally, cardiovascular risk has been associated with three so-called "main" risk factors; hypercholesterolemia, hypertension, and smoking. In addition, the association between diabetes and cardiovascular disease has been known for many years in clinical medicine. Primarily, these risk factors have been regarded separately as independent factors, although epidemiological studies showed intercorrelations between them. However, it is now well accepted that relatively few at-risk individuals have only one risk factor, and in many cases a whole "symphony" of factors play together to create what we might call an individuals' risk profile. As an example, very often essential hypertension has been regarded as a disease in itself, which can be successfully treated just by lowering the blood pressure by drugs. When such a strategy obviously failed, the association of elevated blood pressure with dyslipoproteinemia and impaired glucose tolerance attracted more attention, particularly when it was realized that many antihypertensive drugs affected risk in MCVS in a possible negative way. The most important etiologic factor of MCVS is (besides genetics) an excessive caloric intake compared to what the individual spends in physical activity. In the clinical setting, the most important findings of MCVS are central obesity, dyslipoproteinemia with low high-density lipoprotein (HDL) cholesterol, hypertension, reduced insulin sensitivity in peripheral tissues, and increased thrombogenicity. The reduced insulin sensitivity leads to a compensatory increase in beta-cell insulin production, and thereby hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The metabolic cardiovascular syndrome: syndrome X, Reaven's syndrome, insulin resistance syndrome, atherothrombogenic syndrome. 128 71

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Insulin resistance and hyperinsulinemia is now recognized in non-insulin-dependent diabetes, essential hypertension, obesity, atherosclerotic heart disease, dyslipidemia, heart failure, and in heavy smokers. Several mechanisms have been proposed to explain hyperinsulinemia, insulin resistance and its relationship to hypertension; reduced sodium excretion, activation of the sympathetic nervous system, increased activity of the sodium/hydrogen pump, and stimulation of cellular growth. Some of the nonpharmacological methods to control hyperinsulinemia are of benefit in the management of hypertension, most notably weight loss, exercise program, and reduced salt intake. High-fiber and reduced-protein diets also reduce hyperinsulinemia. Thiazide diuretics can result in insulin resistance, and insulin secretion may be inhibited, possibly associated with concomitant hypokalemia. beta-Blockers result in some reduction of glucose tolerance and mask some of the features of hypoglycemia. Angiotensin-converting enzyme (ACE) inhibitors and alpha-receptor blockers do not effect insulin resistance; probably the same is true for calcium antagonists. Although the effect on risk factors should not be discounted, it is the effect of treatment on hard end points, cerebrovascular accidents, myocardial infarction, or death that is most important. Evidence in hypertension is at present restricted to diuretics and beta-blocking drugs.
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PMID:Hypertension and insulin resistance. 128 47

Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients.
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PMID:Hyperinsulinemia, insulin resistance and essential hypertension. 130 12

Although essential arterial hypertension is believed to have a strong genetic predisposition, the gene(s) responsible are unknown. The mechanisms underlying the regulation of blood pressure and experimental studies place the renin gene among the main candidate genes that need to be tested in humans. We tested the hypothesis of a linkage between the renin gene and essential hypertension using the affected sib pair method. Siblings (133 subjects, 52.1 +/- 10.9 years) from 57 families were selected for sustained hypertension (160.7 +/- 22.9/99.5 +/- 12.8 mmHg with 80% of patients under antihypertensive treatment), of early onset (40.7 +/- 12.0 years), in the absence of obesity, diabetes mellitus, and secondary hypertension. Eight renin haplotypes were generated from three diallelic renin restriction fragment length polymorphisms (RFLPs) (TaqI, HinfI, HindIII) located throughout the renin gene. The allelic concordance between the sib pairs was analyzed by identity by state relationships for 98 sib pairs (41 for 41 couples, 39 for 13 trios, 18 for 3 quartets). Allelic frequencies in the 57 hypertensive probands were similar to those observed among 102 hypertensive subjects studied previously. Six of eight possible haplotypes were observed, the informativity of the marker corresponded to 70% of heterozygosity. Allelic concordance for all sib pairs according to sibship size was not significantly different from that expected under the hypothesis of no linkage (t = 0.52, P = 0.15) reflecting only a small excess of renin alleles shared by the hypertensive sibs (1.44 +/- 0.6 vs 1.36 +/- 0.6). Likewise the linkage hypothesis was unsupported by weighted estimates to correct for possible bias due to large sibship size. Thus, the sib pair analysis suggests that the renin gene does not have a frequent role in the pathogenesis of essential hypertension; further more powerful linkage studies or other approaches will be needed to detect contributions at the renin locus to the heritability of essential hypertension.
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PMID:Sib pair linkage analysis of renin gene haplotypes in human essential hypertension. 134 86

Both haemodynamic and metabolic variables have been shown to be related to the fibre composition and capillary density of skeletal muscle in man. In the present study, the change of several metabolic variables during beta-blockade was investigated and related to muscle fibre composition and capillary density in 28 men with essential hypertension. They had been given atenolol (50 mg/day) or metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months. Serum triglycerides increased during treatment and individual changes were significantly inversely correlated with capillary density. Insulin concentrations in the fasting state and at the end of an i.v. glucose tolerance test were significantly higher during beta-blockade, and individual changes were inversely correlated with capillary density. Furthermore, body weight increased and heart rate decreased, changes that were also correlated with capillary density. It is concluded that many of the previously but poorly understood large interindividual differences in response to beta-blocker treatment may be explained by the degree of development of the capillary net in muscle tissue. Obesity, physical training as well as genetic factors are known determinants of capillary density.
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PMID:The metabolic and circulatory response to beta-blockade in hypertensive men is correlated to muscle capillary density. 136 76

We have investigated the cellular basis for the clinical and epidemiologic linkage of hypertension, left ventricular hypertrophy (LVH), obesity, and non-insulin-dependent diabetes mellitus (NIDDM) and have studied cytosolic free calcium and free magnesium levels in these syndromes. Specifically, intracellular free calcium is elevated and free magnesium is deficient in hypertension, and both are related (directly and inversely, respectively) to the ambient level of blood pressure, to LV mass index (and thus to the degree of cardiac hypertrophy), and to the hyperinsulinemia and insulin resistance of essential hypertension. Dynamically, the ability of dietary salt loading to elevate blood pressure corresponds to its ability to elevate cytosolic free calcium and reciprocally to suppress free magnesium levels. Conversely, the ability of calcium channel blockade to reverse salt-induced hypertension is related to its ability to prevent these transmembrane ionic effects. Higher steady-state free calcium or lower free magnesium, or both, are also observed in clinical states linked to hypertension, such as obesity and NIDDM. Oral glucose loading in normal subjects itself elevates free calcium and suppresses free magnesium levels, as does hyperglycemia in vitro. These data suggest an ionic hypothesis of cardiovascular and metabolic disease, in which a generalized defect in cell ion handling is present in all tissues, resulting in higher steady-state free calcium and lower free magnesium levels. In pancreatic beta cells, this would produce hyperinsulinemia; in fat and skeletal muscle, cause peripheral insulin resistance; and in renal tissue, increase proximal sodium resorption and increase urinary calcium excretion--all features of essential hypertension. In vascular smooth muscle, high cytosolic free calcium would increase smooth muscle tone and cause vasoconstriction, and in heart muscle, independent of blood pressure, would increase contractility and predispose to LVH. Therefore, what may appear clinically to be the separate syndromes of hypertension, obesity, and NIDDM may pathophysiologically be different manifestations of the same underlying cellular defect, thus explaining their frequent clinical coexistence. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion-specific agents, such as calcium channel blocking drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent excess morbidity and mortality of the concurrent cardiac, vascular, and metabolic aspects of the hypertensive state.
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PMID:Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders. 138 62

Changes in both calcium and insulin metabolism have been described in essential hypertension. Low levels of plasma ionized calcium (Ca2+) and high levels of insulin have previously been associated with vascular complications and coronary heart disease. In the present study, indices of calcium metabolism and fasting serum insulin were related to electrocardiographic (ECG) variables in 58 patients with untreated hypertension. Fasting insulin was found to be related to heart rate (r = 0.47, P < 0.001), diastolic interval (r = -0.39, P < 0.004) and electrical axis (r = -0.29, P < 0.03) while Ca2+ was found to be correlated with the QRS amplitude (r = -0.32, P < 0.03) and diastolic interval (r = 0.37, P < 0.02). Furthermore, non-ionized serum calcium was correlated with the QRS duration (r = 0.36, P < 0.02), ST-segment interval (r = -0.49, P < 0.002) and QT interval (QoT, r = -0.42, P < 0.008). These correlations were still significant when the influences of age, sex, obesity, blood pressure and heart rate were taken into account in the multiple regression analysis. In conclusion, the present study demonstrates that calcium and insulin metabolism are related to several basic characteristic functions of the heart, such as the systolic and diastolic function, as well as to signs of left ventricular hypertrophy.
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PMID:Fasting insulin, calcium metabolism and the electrocardiogram in hypertensive subjects. 850 22

Under resting conditions obese hypertensive patients have been described as having a greater cardiac output and lower total peripheral resistance than lean hypertensive patients. To evaluate the hemodynamic patterns under stress conditions, we determined the hemodynamic response to mental stress (first study) and during isometric exercise (second study) in hypertensive patients with a body mass index > 27 kg/m2 (obese) and < 27 kg/m2 (lean). The cohort exposed to mental stress comprised 54 white male patients (30 were lean, 24 were obese) with untreated stage I or II essential hypertension according to the World Health Organization. Obese subjects responded with a higher increase in total peripheral resistance (p < 0.02) and lower increases in heart rate (p < 0.01), cardiac output (p < 0.01) and stroke volume (p < 0.02) when compared with their lean counterparts. This was independent of any differences in chemical or baseline hemodynamic characteristics at rest. The cohort exposed to isometric stress consisted of 57 patients (30 were lean, 27 were obese) with World Health Organization stage I or II essential hypertension. Obese subjects responded with exaggerated increases in systolic (p < 0.04) and diastolic (p < 0.01) pressures, and heart rate (p < 0.04) when compared with lean patients. Body mass index emerged as an independent determinant of the increase in systolic (r = 0.03) and diastolic (r = 0.01) pressure as well as of heart rate (r = 0.03). These results indicate that obese hypertensive patients respond to (1) mental stress with vasoconstriction instead of the expected vasodilation, and to (2) isometric stress with an exaggerated increase in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stress response pattern in obesity and systemic hypertension. 141

The incidence of hypertension is increased in obesity, a state associated with an insulin resistance syndrome. By using an euglycemic clamp method, Ferrannini et al. demonstrated the existence of an insulin resistance state in patients with essential hypertension. However, the body mass index of the subjects studied appeared to be slightly excessive. This abnormality has not been observed in patients with secondary hypertension. Insulin resistance is probably localized to peripheral tissues such as muscles and may be associated with other cellular abnormalities. Can insulin resistance, characterized by a raised circulating insulin concentration in the presence of normal blood glucose, be responsible for certain "modifications" associated with essential hypertension? Insulin induces sodium retention and increases the aldosterone-secreting effect of angiotensin II. These effects are likely to promote a rise in blood pressure and an increase in the sensitivity of vessels to endogenous substances. Moreover, insulin is a known growth factor and is involved in lipoprotein metabolism. If insulin resistance plays an important role in the maintenance of complications of essential hypertension, it is important that the treatments used tend to correct this anomaly. Thiazide diuretics and beta-blockers aggravate insulin resistance while angiotensin converting-enzyme inhibitors correct this condition.
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PMID:[Arterial hypertension, hyperinsulinism and insulin resistance]. 143


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