Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OBESITY AND RISK OF MORBIDITY: Obesity is becoming an increasingly important factor in the pathogenesis of hypertension, dyslipidemia and diabetes, which together with hyperinsulinemia comprise the deadly quartet of the insulin resistance syndrome. Obesity in the absence of these other factors is only a minor risk factor, but most obesity is accompanied by one or more of these, worsening the prognosis. The presence of obesity complicates the management of hypertension, probably in large part because of the concomitant insulin resistance which adds to the pathogenetic mechanisms and subtracts from the therapeutic efficacy of many antihypertensive regimens. Unfortunately, some of the agents used to reduce obesity may further aggravate the problem through their stimulation of sympathetic nervous activity. Nonetheless, in the treatment of hypertension in most obese patients who have relatively little excess risk, attempts to reduce body weight should be attempted first, through sensible dietary restrictions, increased aerobic exercise and judicious use of non-hypertensinogenic appetite suppressants. Thereby, additional motivation to lose weight may be provided by the potential of escaping or at least delaying antihypertensive drug therapy. TREATMENT OF HIGHER-RISK OBESE INDIVIDUALS: Those obese hypertensive individuals at greater risk should be immediately started on antihypertensive drug therapy along with attempts to reduce the obesity. The choice of initial and subsequent therapy should take the patient's individual needs into account. For those with dyslipidemia or diabetes, diuretics and beta-blockers should be avoided unless there are specific indications for their use (e.g. reactive sodium retention or postmyocardial infarction). In such patients, an alpha-blocker, an angiotensin converting enzyme inhibitor or a calcium antagonist may be more appropriate. If the first drug is not sufficient, combination therapy should be considered. A diuretic may be needed to overcome reactive sodium retention. Because most obese hypertensive individuals will not be able to lose much weight, effective antihypertensive drug therapy will usually be indicated.
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PMID:Obesity in hypertension: effects on prognosis and treatment. 953 95

Rilmenidine is an antihypertensive agent with selectivity for I1 imidazoline receptors that acts both centrally by reducing sympathetic overactivity and in the kidney by inhibiting the Na+/H+ antiport. Rilmenidine provides antihypertensive efficacy comparable with that of diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Experience from trials and clinical practice highlights rilmenidine's clinical and metabolic acceptability in hypertensive populations, including those at special risk because of old age, renal impairment, diabetes mellitus, or dyslipidemia. In the at-risk hypertensive, rilmenidine reduces left ventricular hypertrophy to a similar degree to other reference agents. New studies show a significant improvement in glucose metabolism in metabolic syndrome patients treated with rilmenidine, and a significant reduction in microalbuminuria during rilmenidine treatment of hypertensive type 2 diabetics. Thus the efficacy/tolerance ratio of rilmenidine supports its role as a first-line antihypertensive option for all groups of hypertensive patient, with specific advantages in some at-risk populations.
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PMID:Rilmenidine: a clinical overview. 1092 29

Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.
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PMID:The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin. 1095 86

Weight reduction diets may reduce the severity of risk factors for coronary heart disease such as diabetes mellitus, hypertension, and dyslipidemia. Several case reports and small studies of patients receiving starvation diets have reported hypotension and sudden cardiac death. Myofibrillar damage was documented in 1 case. Very-low-calorie diets are generally safe and well-tolerated. However, low QRS voltage, QT interval prolongation, and both nonsustained ventricular arrhythmias and sudden cardiac death have been described in subjects treated with such diets. Orthostatic hypotension may complicate very-low-calorie protein diets because of sodium depletion and depressed sympathetic nervous system activity. Bariatric surgery is associated with disproportionately high mortality rates in both the perioperative and postoperative periods.
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PMID:Cardiovascular complications of weight reduction diets. 1130 68

Intentional weight loss improves many of the medical complications associated with obesity. Moreover, many of these beneficial effects have a dose-dependent relationship with the amount of weight lost and begin after only modest weight losses of 5% to 10% of initial body weight. There is no conclusive evidence that weight loss decreases mortality in obese people. The therapeutic effect of weight loss on risk factors for cardiovascular disease (insulin resistance and diabetes, dyslipidemia, and hypertension) has received the most attention in clinical trials. The hazard of developing coronary heart disease is directly related to the concomitant burden of risk factors. Modest weight loss can affect the entire cluster of risk factors simultaneously. Both negative energy balance and weight loss improve insulin sensitivity and glycemic control in obese patients with type 2 diabetes. Most studies have found that weight loss decreases serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol concentrations and increases serum high-density lipoprotein cholesterol concentration. Regain of weight leads to relapse in triglyceride and cholesterol concentrations. Weight loss, independent of sodium restriction, decreases systolic and diastolic blood pressure. Dietary intervention is the cornerstone of weight-loss therapy. Most diets proposed for losing weight vary in two principal dimensions: energy content and macronutrient composition. Manipulation of food macronutrient content, energy density, and portion size can help decrease energy intake and facilitate weight loss.
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PMID:Outcome success in obesity. 1170 65

There are several reports in literature implicating cholesterol metabolism in the pathogenesis of neuronal degenerations, oncogenesis, functional neuropsychiatric disorders and multiple sclerosis. Biosynthesis of cholesterol takes place by the isoprenoid pathway, which also produces digoxin, an inhibitor of membrane Na(+)-K+ ATPase. Inhibition of this enzyme results in intracellular Mg++ deficiency which can influence cholesterol metabolism. Digoxin also influences transport of tryptophan and tyrosine which are precursors of various neurotransmitters. Alterations in digoxin, membrane Na(+)-K+ ATPase and also in neurotransmitters have been reported in the disorders mentioned above. In view of this, serum lipid profile, activity of plasma HMG CoA reductase (the major rate limiting step in the isoprenoid pathway), RBC membrane Na(+)-K+ ATPase activity, serum Mg++ concentration, concentration of digoxin and concentration of serum neurotransmitters were studied in some neuropsychiatric disorders. The serum serotonin level was increased while that of serum dopamine and noradrenaline was reduced. Serum digoxin levels were high and RBC membrane sodium-potasium ATPase activity and serum magnesium were reduced. There was a reduction in HDL cholesterol and increase in plasma triglycerides (pattern similar to insulin resistance and syndrome X) in most of the disorders studied. The HMG CoA reductase activity was high, the serum total cholesterol was increased while RBC membrane cholesterol was reduced in most of the cases. The significance of increased digoxin with consequent inhibition of membrane Na(+)-K+ ATPase in relation to changes in cholesterol metabolism and insulin resistance type of dyslipidemia is discussed in this paper.
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PMID:Membrane Na+ K+ ATPase inhibition related dyslipidemia and insulin resistance in neuropsychiatric disorders. 1188 68

The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms.
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PMID:Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine. 1281 13

Subclinical hypothyroidism (sHT) is associated with enhanced cardiovascular risk. To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide (NO) availability, in 14 patients [serum cholesterol, 218 +/- 41 mg/dl (5.6 +/- 0.9 mM)] and 28 euthyroid subjects, subdivided into groups A and B [serum cholesterol, 170 +/- 19 mg/dl (4.4 +/- 0.5 mM) and 217 +/- 21 mg/dl (5.6 +/- 0.5 mM), respectively], we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine, an endothelium-dependent vasodilator, at baseline and during infusion of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor. Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated. In sHT patients, vasodilation to acetylcholine was reduced, compared with group B (+358 +/- 29% vs. +503 +/- 19%, P = 0.0003) and group A (663 +/- 65%, P = 0.02 vs. group B and P = 0.0002 vs. sHT). L-NMMA blunted the vasodilation to acetylcholine in groups A and B (49.1 +/- 6.3% and 42.7 +/- 5.5% maximal forearm blood flow reduction, respectively, P < 0.0001 vs. acetylcholine), whereas it was ineffective in sHT patients (12.8 +/- 2.5%). Response to sodium nitroprusside and minimal vascular resistances were similar. In sHT (n = 9) patients, 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition. Patients with sHT are characterized by endothelial dysfunction resulting from a reduction in NO availability, an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation.
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PMID:Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. 1291 62

The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol), elevated blood pressure, impaired glucose tolerance, and central obesity is identified now as metabolic syndrome, also called syndrome X. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the U.S. population. The National Cholesterol Education Program-Adult Treatment Panel III has identified metabolic syndrome as an indication for vigorous lifestyle intervention. Effective interventions include diet, exercise, and judicious use of pharmacologic agents to address specific risk factors. Weight loss significantly improves all aspects of metabolic syndrome. Increasing physical activity and decreasing caloric intake by reducing portion sizes will improve metabolic syndrome abnormalities, even in the absence of weight loss. Specific dietary changes that are appropriate for addressing different aspects of the syndrome include reducing saturated fat intake to lower insulin resistance, reducing sodium intake to lower blood pressure, and reducing high-glycemic-index carbohydrate intake to lower triglyceride levels. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with metabolic syndrome. Family physicians can be more effective in helping patients to change their lifestyle behaviors by assessing each patient for the presence of specific risk factors, clearly communicating these risk factors to patients, identifying appropriate interventions to address specific risks, and assisting patients in identifying barriers to behavior change.
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PMID:Metabolic syndrome: time for action. 1522 52

Overweight/obesity represent an underestimated risk factor of renal disease. The incidence of obesity-related glomerulopathy (ORG) tremendously increased within the last decade. The first sign of renal damage in overweight conditions is microalbuminuria or proteinuria, indicating the potential risk of its progression to renal insufficiency and the development of premature cardiovascular events. In the early stage of obesity renal hemodynamics are characterized by a renal hypercirculation and glomerular hyperfiltration, particularly in the presence of hypertension. The hyperfiltration is especially harmful in patients with pre-existing inflammatory and metabolic renal disease, or under the conditions of reduced renal mass. Histopathologically, ORG is characterized by glomerulomegaly with/without signs of focal segmental glomerulosclerosis. Pathogenetically, numerous factors are involved, e.g. enhanced glomerular capillary pressure, adrenergic nerve overactivity, inappropriate activation of the renin-angiotensin-aldosterone system, insulin resistance, hyperinsulinemia and hyperleptinemia, dyslipidemia, enhanced clotting tendency and sodium retention. Diabetic nephropathy is one of the most serious complications of obesity-induced diabetes. In the industrial nations type 2 diabetes is the single most frequent cause of end-stage renal disease. After kidney transplantation, overweight/obesity is associated with a less favourable prognosis for the survival of the graft and the patient. Incidence of renal cell carcinomas is enhanced in overweight/obesity. Obesity-related renal disease may be prevented/postponed by an early weight reduction, by dietary intervention combined with physical exercise. In the advanced stages of renal disease benefits of weight reduction are minimal. Concomitant administration of angiotensin-converting-enzyme inhibitors or angiotensin II receptor 1 blockers exerts antiproteinuric effects and thereby aid in retarding the disease progression. Aimed prevention and treatment of obesity represent a challenge for the healthcare system. The concerted action of physicians, patients and the public health authorities is needed.
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PMID:[Overweight and obesity--risk factors in the development and progression of renal disease]. 1532 63


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