Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Hypertension is the commonest cardiovascular disease in Africans occurring in more than 15% of the adult population in some studies. It occurs in the lower as much as in the higher socio-economic groups. Recent studies have confirmed earlier findings that essential hypertension in Africans is characterised by volume loading, low plasma renin activity, high salt taste threshold, high urinary sodium and low potassium excretion and high plasma aldosterone. The commonest complication of hypertension in Africans is congestive cardiac failure followed by cerebrovascular accidents. Coronary heart disease is rare. Even in the absence of overt heart failure and compounding factors like obesity, alcoholism, cigarette smoking, diabetes mellitus and myocarditis, evidence of abnormal left ventricular morphology and function is often present in newly diagnosed patients with moderate or severe hypertension. Response to monotherapy with beta-blockers or ACE inhibitors is usually poor but is good with thiazide diuretics or calcium channel blockers. The diuretics are an essential component of a two or three drug regime containing other classes of antihypertensive drugs. Cost of drugs is the most important determinant of compliance with drug treatment and consequently the likelihood of progression of the diseases to more severe forms in long term follow-up.
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PMID:Hypertension in Africa and effectiveness of its management with various classes of antihypertensive drugs and in different socio-economic and cultural environments. 826 3

Secondary causes of hyperlipidemia are important to recognize. In fact, hyperlipidemia may be a clue to the presence of an underlying systemic disorder. It may greatly heighten the risk of atherosclerosis with a raised LDL-c, triglyceride-rich lipoprotein excess, and increased lipoprotein(a) as well as lowered HDL-c. The search for secondary causes may provide a clue as to why patients with primary lipid disorders suddenly develop worsening lipid profiles. The point is a crucial one because some acquired causes of hyperlipidemia, such as alcohol, estrogens, steroids, or pregnancy, when superimposed on a primary familial form of hypertriglyceridemia can result in a saturated removal system and a buildup of chylomicrons, which can lead to life-threatening pancreatitis. A convenient way to remember secondary causes is to think of the four D's of diet, drugs, disorders of metabolism, and diseases. Although diets rich in saturated fats and cholesterol are a common cause of the mild hypercholesterolemia seen in our society, alcohol excess and weight gain can explain much of the tendency toward hypertriglyceridemia. Interestingly anorexia nervosa has long been associated with severe but reversible hypercholesterolemia. Several classes of drugs need to be considered as common causes of altered lipid profiles. Glucocorticoids and estrogens elevate triglycerides and raise levels of HDL-c. Anabolic steroids taken orally markedly reduce levels of HDL-c in contrast to injectable testosterone, which does not adversely affect the LDL-to-HDL ratio. Oral contraceptives affect atherosclerotic risk depending on the kind and doses of progestin/estrogen. In those with an underlying primary hypertriglyceridemia and associated obesity, estrogenic medications can depress triglyceride removal mechanisms, leading to the chylomicronemia syndrome and pancreatitis. Antihypertensives have variable effects on lipids and lipoproteins. Although short-term thiazide usage raises cholesterol, triglycerides, and LDL-c, long-term usage is not necessarily associated with significant alterations in lipid levels. Alpha blockers may cause an increase in HDL-c, whereas beta blockers raise triglycerides and lower HDL-c. Sympatholytics, angiotensin converting enzyme inhibitors, and calcium channel blockers are essentially lipid neutral. Retinoids can be associated with increased LDL-to-HDL ratios and occasionally striking elevations in triglycerides. Cyclosporine raises LDL-c and lipoprotein(a). Classes of drugs that may raise HDL-c include cimetidine, antiepileptic drugs, and tamoxifen, but the effect may be seen primarily in women. Hypothyroidism is the most common secondary cause of hyperlipidemia after dietary causes are considered. A thyroxine and TSH level should be obtained on all new cases of clinically important hyperlipidemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Secondary causes of hyperlipidemia. 828 27

Mutations leading to ectopic expression of the murine agouti gene (a) result in progressive obesity. To further characterize this model, we analyzed adipose and hepatic mRNA levels for fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD), two key enzymes in de novo fatty acid synthesis and desaturation, respectively. FAS and SCD mRNA in both tissues of obese (Avy) mice were dramatically increased relative to lean (ala) controls. Excessive expression of these genes in this model could be due to direct effects of the agouti gene product; to test this possibility we treated 3T3-L1 adipocytes in vitro with recombinant agouti protein. Agouti treatment increased FAS and SCD mRNA levels by 1.5- and 4-fold, respectively. In addition, FAS activity and triglyceride content were 3-fold higher in agoutitreated 3T3-L1 cells relative to controls; these effects were attenuated by simultaneous treatment with a calcium channel blocker (nitrendipine). These data demonstrate that the agouti protein can directly increase lipogenesis in adipocytes and suggest that these effects are mediated through an intracellular calcium-dependent mechanism.
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PMID:Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity. 877 92

Diabetes mellitus and hypertension each confer increased cardiovascular risk. That risk is much greater when the diseases coexist and is further magnified by their frequent association with dyslipidemia and central obesity. Insulin resistance appears to be an important common component to these four entities, whether or not the relationship is truly cause and effect. Increased renal tubule absorption of sodium and increased sympathetic nervous system stimulation from insulin have been said to be the mechanisms by which elevated levels of insulin cause hypertension. However, animal experiments suggest that these are short-term effects only and that long-term insulin may actually increase peripheral blood flow and reduce blood pressure. Experiments in humans suggest that the insulin resistant state in obese patients and type II diabetics is associated with a decrease of the usual vasodilatory effect of insulin. Antihypertensive drugs have differing effects on insulin resistance. Angiotensin converting enzyme inhibitors, alpha-adrenergic blockers, and dihydropyridines appear to improve insulin sensitivity. Other calcium channel blockers appear to be neutral, as is furosemide. Thiazide diuretics, spironolactone, and beta-adrenergic blockers impair insulin sensitivity. The drugs that increase insulin sensitivity also tend to improve dyslipidemia or remain lipid neutral. In contrast, those drugs that tend to impair insulin sensitivity also tend to worsen dyslipidemia.
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PMID:Hypertension in patients with diabetes mellitus. 884 91

The JCR:LA-cp rat exhibits the obesity/insulin resistance/hypertriglyceridemia syndrome in an extreme form. These normotensive rats spontaneously develop advanced atherosclerosis and ischemic myocardial lesions. The calcium channel antagonist, nisoldipine, was administered to obese rats of the JCR:LA-cp strain in drinking water at a dose of 1 mg/kg from age 6 weeks. Nisoldipine-treated rats showed no change in food consumption or body weight compared with control animals. Plasma glucose and insulin levels also were unchanged in the nisoldipine-treated rats. Insulin-mediated total glucose turnover, an index of insulin sensitivity as measured by euglycemic insulin clamp, was similarly not improved. Serum triglyceride levels in obese male rats were markedly reduced (57%; p < 0.001, at age 12 weeks), whereas obese female rats showed no significant change in triglyceride levels and an increase in esterified cholesterol in response to nisoldipine treatment. The impaired endothelium-dependent (nitric oxide-mediated) vascular relaxation of the male cp/cp rats was not improved by nisoldipine treatment. The severity of atherosclerotic raised lesions in the aortic arch of male cp/cp rats was significantly reduced (p < 0.01) by nisoldipine treatment, and this was accompanied by a major reduction in the incidence of ischemic myocardial lesions (85%; p < 0.01). Thus nisoldipine treatment ameliorates atherosclerotic damage and myocardial injury even in the presence of gross obesity, hyperinsulinemia, and significant hyperlipidemia. This effect appears to involve protection of the vascular wall from atherogenesis and probably antivasocontractile effects at the smooth muscle level as well.
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PMID:Cardioprotective and hypolipidemic effects of nisoldipine in the JCR:LA-cp rat. 921 99

Between January 1990 and May 1995, 117 patients were admitted to the Intensive Care Unit at Holberton Hospital, Antigua, for chest pain due to suspected acute myocardial infarction. 39 (45%) of 86 patients whose records were available for retrospective review had confirmed (27 patients) or probable (12 patients) acute myocardial infarction. Risk factors identified among the patients included hypertension, diabetes, tobacco smoking, hypercholesterolaemia and obesity. On admission, 82% were Killip class I and 18% were Killip class II. Medications in the Intensive Care Unit included nitrates, aspirin, calcium channel blockers, beta-adrenergic blockers, heparin and angiotensin converting enzyme inhibitors (21%). No thrombolytic agents were available. The average hospital stay was 10 days and the in-hospital mortality rate was 13%. These data indicate that early mortality from acute myocardial infarction can be reduced in developing countries by early admission to an Intensive Care Unit and use of drugs known to be effective in its treatment.
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PMID:Myocardial infarction in Antigua. 1990 to 1995. 936 95

Essential hypertension appears to be more prevalent among blacks than among whites and has an earlier onset in blacks. Many data in this field come from studies in the African-American population. Hypertension-related complications, e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular disease, are encountered more often among blacks and frequently run a more severe course. Factors that might explain the racial difference in prevalence of hypertension and hypertensive complications include both genetic and environmental variables. Hypertension in blacks is characterized by salt sensitivity, a tendency towards expanded plasma volume and low plasma renin levels. Socioeconomic factors, the higher prevalence of obesity and insulin resistance may contribute to the high prevalence of hypertension in blacks. Aggressive antihypertensive therapy appears mandatory in the black hypertensive, possibly with lower goal blood pressures than the 140/90 mmHg generally recommended. Diuretic monotherapy proves to be the first-line therapy, calcium channel blockers are an attractive alternative. Black patients are frequently less responsive to monotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blocking agents. This black/white difference in therapeutic response can, however, be eliminated by addition of a diuretic.
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PMID:[Hypertension in the Negro patient]. 1008 50

This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 +/- 0.32 (mean +/- SEM) to 3.97 +/- 0.31 mg/kg/min (P = .02). A similar tendency was observed with enalapril: from 3.59 +/- 0.32 to 3.94 +/- 0.30 mg/kg/min (P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 +/- 0.11 to 1.39 +/- 0.13 with amlodipine (P = .03) and from 1.25 +/- 0.13 to 1.49 +/- 0.16 with enalapril (P = .01). LDL cholesterol decreased with amlodipine (mean change, -11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.
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PMID:A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients. 1019 33

A retrospective review of the cases of congestive heart failure admitted to Holberton Hospital in Antigua in 1995 and 1996 was undertaken. Two hundred and ninety-three (293) patients were identified by International Statistical Classification of Diseases, 10th revision (ICD-10) coding as having congestive cardiac failure in the period but only 138 charts were either available or fitted the definition of congestive cardiac failure and these provided the basis for this analysis. The average age of patients admitted for congestive cardiac failure was 69 years (range: 5 months to 99 years), and 63% were female. the aetiology of congestive cardiac failure was hypertension (41%), ischaemia (33%), valvular (12%), alcohol related (2%), idiopathic (5%) and mixed (7%). Treatment included diuretics (95%), angiotensin converting enzyme inhibitors (78%), digoxin (75%), nitrates (34%), calcium channel blockers (25%), other vasodilators (7%) and antiarrhythmics (5%). Of those with congestive heart failure, diabetes was present in 38%, atrial fibrillation in 19%, renal insufficiency in 17%, elevated cholesterol in 11%, obesity in 9% and tobacco use in 7%. The in-hospital mortality in the 2-year period was 17.4% (females 15%, males 22%, 11% < 65 years, 20% > 65 years, 14% for those with 1 to 3 admissions and 83% for those with > 3 admissions, 19% for those with atrial fibrillation and 16% for those without). The prevalence of congestive cardiac failure utilizing the data analysed in this study (138 patients) was 0.21% of the population of the island state but based on the discharge diagnosis using ICD-10 coding it was 0.5%; it was 1% in the 40 to 65-year-age group and 4% in those > 65 years of age. The patients in this study represented only those with New York Heart Association (NYHA) classes III and IV, hence the true prevalence would be higher than recorded here. Congestive cardiac failure is emerging as a significant health problem in Antigua and Barbuda.
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PMID:The prevalence, aetiology and treatment of congestive cardiac failure in Antigua and Barbuda. 1055 60

The association of obesity and hypertension is characterized hemodynamically by an increase in absolute circulating intravascular volume that induces increased cardiac output and total peripheral resistance that remains inappropriately normal. These changes constitute the hemodynamic basis for the increase in blood pressure in obesity. Obesity-associated hypertension is also characterized by an abnormal renal response, including increased renal blood flow and a rise in glomerular and interstitial pressures. These hemodynamic changes induce the following structural changes in the heart: enlarged left atrial, ventricular and aortic root diameters as well as increased posterior septal wall thickness and left ventricular mass. The hemodynamic changes in the kidneys generate higher glomerular volume and increased interstitial infiltrate, which may cause compression of the tubules and blood vessels of the renal medulla. Weight reduction is an effective tool in the control of blood pressure, and significantly reduces the metabolic and hemodynamic derangements that occur with obesity. However, since weight reduction compliance is difficult to maintain, pharmacological agents are often needed to control blood pressure. Angiotensin-converting enzyme inhibitors, calcium channel blockers and alpha- adrenergic blocking agents may be the most appropriate therapy for obesity-associated hypertension since they intervene with some of the previously described pathophysiological conditions.
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PMID:Obesity-associated hypertension: hypothesized link between etiology and selection of therapy. 1082 14


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