Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it.
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PMID:Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. 1241 79

Obesity is a major chronic health problem in adults. It is a complex, multifactorial disorder characterised by excess accumulation of adipose tissue. It is associated with a number of complications including cardiovascular disease, hypertension, type 2 diabetes, dyslipidaemia and cancer. A weight loss in the order of 5-10% is associated with clinically meaningful reductions with respect to all comorbidities. Diet and exercise has been the cornerstone of weight management therapy, but this approach has limitations, especially for weight maintenance. Previous drugs used in obesity had serious side effects including valvular heart disease. However, recent drugs like orlistat and sibutramine have been rigorously tested and proven safe. Orlistat, a lipase inhibitor, inhibits absorption of dietary fat by approximately 30%. Taken with a hypocaloric diet, it produces and maintains clinically meaningful weight loss. Sibutramine is a centrally-acting agent which enhances satiety and thermogenesis by inhibiting serotonin and noradrenaline re-uptake. It is appropriate for patients who are unable to lose weight by lifestyle modification.
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PMID:Pharmacological management of obesity. 1247 68

Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in conjunction with appropriate dietary control, for the treatment of obesity. It is generally deemed to be a safe drug, which mainly exerts a topical action on the stomach and small bowel, with negligible systemic absorption and oral bioavailability. Consequently, its adverse effects have largely been limited to relatively mild gastrointestinal disorders. However, there have been recent, published reports of non-fatal acute hepatitis and systemic hypertension associated with its use. The present case concerns a 62-year-old male who died from massive hepatocellular necrosis, consistent with drug-induced, fulminant hepatitis, associated with the use of oral orlistat, presumably administered at the recommended daily dose of 360 mg. It is postulated that this may represent a rare idiosyncratic reaction to the drug.
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PMID:Massive hepatocellular [correction of hepatocullular] necrosis: was it caused by Orlistat? 1248 15

Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors. Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, beta-fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.
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PMID:Genetic polymorphisms in emerging cardiovascular risk factors and response to statin therapy. 1284 89

The level of fatness of a child at which morbidity acutely increases is operationally determined by calculating the body mass index (BMI). An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been > 75(th) percentile as adolescents. Childhood obesity seems to substantially increase the risk of subsequent morbidity whether or not obesity persists into adulthood. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidaemia, back pain and psychosocial problems. Environmental/exogenous factors largely contribute to the development of body fatness early in life. Therapeutic strategies include psychological and family therapy, lifestyle/behaviour modification and nutrition education. The role of regular exercise and exercise programmes is emphasised. Surgical procedures and drugs used in adult obesity are not generally recommended in children and adolescents. Appetite suppressants and thermogenic drugs have not been approved for use in children. Digestive inhibitors such as lipase inhibitors and fat substitutes have been used in children and adolescents in off-label use and in only a few clinical studies. As obesity is the most common chronic disorder in the industrialised societies, its impact on individual lives, as well as on health economics, has to be recognised more widely. One should aim to increase public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic that is present around the globe.
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PMID:Pharmacoeconomics of obesity management in childhood and adolescence. 1294 76

In many industrialized nations, obesity is now considered an epidemic, resulting in accelerated morbidity and mortality. Obesity is associated with an increased risk of coronary artery disease as well as the metabolic syndrome comprising abdominal obesity, increased fasting blood glucose levels, dyslipidemia and hypertension, which are all recognized cardiovascular risk factors. Diet, exercise, and lifestyle changes constitute important recommendations for treatment. Unfortunately, although effective in some individuals, these recommendations have proven to be ineffective in adequately addressing the broad, enlarging scope of this public health problem. Drug treatment is often indicated but is somewhat limited by the minimal number of well tolerated drugs that have proven to have long-term efficacy in maintaining bodyweight loss. For example, phentermine may result in modest bodyweight loss through suppression of appetite, but potential cardiovascular adverse effects exist and the efficacy is mainly short-term. Sibutramine, an inhibitor of serotonin and norepinephrine (noradrenaline) reuptake, may increase satiety and result in modest bodyweight loss. However, cardiovascular adverse effects may occur in susceptible patients. Nonetheless, sibutramine is one of the few drugs that has been approved by the US Food and Drug Administration (FDA) for bodyweight loss. Orlistat, a lipase inhibitor, is also approved by the FDA for bodyweight loss but may have bothersome gastrointestinal adverse effects, especially among patients who do not adhere to the recommended low-fat diet. Ongoing studies continue to evaluate other drug treatments that may result in bodyweight reduction through a number of different mechanisms. It is anticipated that the development of effective and well tolerated antiobesity drugs will elevate the pharmacologic treatment of obesity to the status of other cardiovascular risk factors and metabolic disorders. This may be especially important given that dyslipidemia, hypertension and type 2 diabetes mellitus are often secondary to, or exacerbated by, obesity.
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PMID:Pharmacotherapy of obesity: currently marketed and upcoming agents. 1472 70

This Genetic Analysis Workshop 13 contribution presents a linkage analysis of hypertension in the Framingham data based on the posterior probability of linkage, or PPL. We dichotomized the phenotype, coding individuals who had been treated for hypertension at any time, as well as those with repeated high blood pressure measurements, as affected. Here we use a new variation on the multipoint PPL that incorporates integration over the genetic model. PPLs were computed for chromosomes 1 through 5, 11, 14, and 17 and remained below the 2% assumed prior probability of linkage for 73% of the locations examined. The maximum PPL of 4.5% was obtained on chromosome 1 at 178 cM. Although this is more than twice the assumed prior probability of linkage, it is well below a level at which we would recommend committing substantial additional resources to molecular follow-up. While the PPL analysis of this data remains inconclusive, Bayesian methodology gives us a clear mechanism for using the information gained here in further studies.
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PMID:A model-integrated multipoint Bayesian analysis of hypertension in the Framingham Heart Study data finds little evidence of linkage. 1497 43

The two-month effects of dietary fish protein and casein on VLDL, HDL(2) and HDL(3) compositions and hepatic lipase (HTGL) and tissue lipoprotein lipase (LPL) activities were examined in spontaneously hypertensive rats (SHR) at 4 wk of age. After 2 mo of experiment, the fish protein diet induced lower blood pressure (-14 %) as compared to casein. Liver triacylglycerol and total cholesterol concentrations were 1.37- and 1.71-fold lower in the fish protein group than in the casein group, respectively. Total cholesterol concentration in plasma was also diminished by fish protein (-21 %) and was reflected in HDL(2) fraction (-44 %). SHR fed the fish protein diet as compared with those fed casein, showed a significantly low HDL(3) particle number, as measured by diminished HDL(3) mass and apo A-I. The consumption of fish protein did not affect VLDL particle number, but significantly decreased VLDL-triacylglycerol (-32 %) and adipose tissue total lipid concentrations as compared to casein. This was accompanied by diminished HTGL and adipose tissue LPL activities (-10%, -91%, respectively). These data demonstrate that fish protein plays an antihypertensive role and reduces plasma and tissue lipid concentrations. Thus, a fish protein intake might be beneficial for patients with hypertension.
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PMID:Fish protein improves blood pressure but alters HDL2 and HDL3 composition and tissue lipoprotein lipase activities in spontaneously hypertensive rats. 1530 59

We report on a 50-year old man who presented with upper abdominal pain and new T-wave inversions in the anterior leads of the electrocardiogramm. Since the patient additionally had cardiovascular risk factors (positive family history, smoking, hypercholesterinemia and hypertension) he was initially thought to have an acute coronary syndrome. Moreover, he had elevated serum levels of amylase and lipase, and together with typical findings of abdominal ultrasound he was diagnosed with acute pancreatitis responsible for the patient's pain. The ECG changes persisted during the hospital stay, but had fully normalised three weeks later. Further cardiologic evaluation yielded normal results. Thus, the ECG-abnormalities could be attributed to the acute pancreatitis, which can cause ECG-pathologies mimicking an acute coronary syndrome in up to 30%. Knowledge of there findings is important in order to prevent wrong therapeutic decisions.
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PMID:[Epigastric pain and abnormal ECG]. 1577 13

The overweight and obesity represent severe problems for the health management system of developed countries. In the evolution of obesity, beside genetic background, the environmental factors also play important roles. In the daily routine, the majority of obese patients need drug treatment, over the diet and physical activity. Among the available medicines the inhibitors of monoamine re-uptake causes dry mouth, tachycardia, sleeplessness and elevated blood pressure, therefore, due to the frequently associated obesity and hypertension many physicians avoid using these compounds. The orlistat as a selective inhibitor of pancreatic and enteral lipase enzymes impedes the absorption of the highest calorie containing nutrients, the fats exerting beneficial effects in the treatment of obesity. The abdominal bloating and diarrhea as side effects of the drug may act as an advantage in many cases, since these happen especially in those cases when the patient neglects the previously suggested low fat diet and therefore the drug induced diarrhea and bloating may mean a feed-back for the patient in respect of the proper diet. Recent studies show many beneficial biochemical changes in obesity related pathological metabolic processes during the administration of orlistat. The authors, in their present work review in short the role of orlistat in the treatment of slimming cure.
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PMID:[The role of orlistat in the treatment of obesity]. 1581 87


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