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

Obesity, especially upper body fat distribution, has become an increasingly important medical problem in children and adolescents. Outcomes related to childhood obesity include, as in adult population, hypertension, type 2 diabetes mellitus, dyslipidemia, left ventricular hypertrophy, obstructive sleep apnea, orthopedic and socio-psychological problems. Obese children are at approximately 3-fold higher risk for hypertension from non-obese ones. Obesity-hypertension appears to be characterized by a preponderance of isolated systolic hypertension, increased heart rate and blood pressure variability, increased levels of plasma catecholamine and aldosterone, and salt-sensitivity. Lifestyle changes of weight loss, healthier diet and regular physical exercise are effective in obesity-hypertension control, though pharmacological treatment is frequently necessary. Screening for dyslipidemia and impaired glucose tolerance should be performed in paediatric patients with obese hypertension on regular basis, at least once annually or semiannually to discover metabolic syndrome and to prevent its increased cardiovascular risk. Of course, prevention of obesity is the primary goal.
 ...
PMID:[Hypertension in obese children and adolescents]. 1937 Sep 74

The evidence is compelling for a role of inflammation in cardiovascular diseases; however, the chronic use of anti-inflammatory drugs for these indications has been disappointing. The recent study compares the effects of two anti-inflammatory agents [cyclooxygenase 2 (COX2) and p38 inhibitors] in a model of cardiovascular disease. The vascular, renal, and cardiac effects of 4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one (rofecoxib; a COX2 inhibitor) and 6-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}-N-(2,2-dimethylpropyl)-3-pyridinecarboxamide [GSK-AHAB, a selective p38 mitogen-activated protein kinase (MAPK) inhibitor], were examined in the spontaneously hypertensive stroke-prone rat (SHR-SP). In SHR-SPs receiving a salt-fat diet (SFD), chronic treatment with GSK-AHAB significantly and dose-dependently improved survival, endothelial-dependent and -independent vascular relaxation, and indices of renal function, and it attenuated dyslipidemia, hypertension, cardiac remodeling, plasma renin activity (PRA), aldosterone, and interleukin-1beta (IL-1beta). In contrast, chronic treatment with a COX2-selective dose of rofecoxib exaggerated the harmful effects of the SFD, i.e., increasing vascular and renal dysfunction, dyslipidemia, hypertension, cardiac hypertrophy, PRA, aldosterone, and IL-1beta. The protective effects of a p38 MAPK inhibitor are clearly distinct from the deleterious effects of a selective COX2 inhibitor in the SHR-SP and suggest that anti-inflammatory agents can have differential effects in cardiovascular disease. The results also suggest a method for evaluating long-term cardiovascular efficacy and safety.
 ...
PMID:Differential effects of p38 mitogen-activated protein kinase and cyclooxygenase 2 inhibitors in a model of cardiovascular disease. 1955 50

Regardless of the diagnostic criteria, the metabolic syndrome is found at least in 20% of the population. The adipose tissue plays an important role in the insulin resistance found in this syndrome. Free fatty acids released by intra-abdominal adipocytes produce an inflammatory and pro-thrombotic response and the persistence of the insulin resistance state, phenomenon termed lipotoxicity. This altered phenotype explains the development of the different components of the metabolic syndrome, such as hypertension, dyslipidemia and altered glucose metabolism. The treatment is based on weight loss and healthy lifestyle. A balanced diet, physical activity and avoidance of smoking are key management features. The use of drugs with pleiotropic effects, which inhibit the renin angiotensin aldosterone axis or acts on the peroxisome proliferators-activated receptors (PPAR) seems promising.
 ...
PMID:[Metabolic Syndrome: clinical and pathophysiological basis for a rational therapeutical approach]. 1970 60

Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: microalbuminuria and macroalbuminuria. The cut-off values of micro- and macroalbuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macroalbuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower normoalbuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyperfiltration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive mesangial expansion (diffuse or nodular) leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the development or progression of the disease and to decrease the subject's increased risk of cardiovascular disease. Achieving the best metabolic control, treating hypertension (<130/80 mmHg) and dyslipidemia (LDL cholesterol <100 mg/dl), using drugs that block the renin-angiotensin-aldosterone system, are effective strategies for preventing the development of microalbuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with diabetes.
 ...
PMID:Diabetic nephropathy. 1982 47

The Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is exploring two pharmacological strategies (nateglinide and valsartan, both alone and in combination) in the prevention of overt diabetes mellitus (DM) and the reduction of cardiovascular disease (CVD) in subjects at high risk for these events. In this analysis, we provide baseline characteristics of the randomized NAVIGATOR study population and contrast them with those from other trials of DM prevention. Key eligibility criteria include impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), a history of CVD (in patients aged > or =50 years), and > or =1 cardiovascular risk factor (in patients aged > or =55 years). Baseline demographic characteristics, laboratory findings, cardiovascular risk factors, CVD history, and medication use are described and compared with other trials of DM prevention. The full analysis set of subjects (N = 9306) showed a clustering of risk factors consistent with the metabolic syndrome: high rates of hypertension (77.5%), dyslipidemia (44.7%), increased waist circumference (101.0 cm), and high body mass index (BMI) (47.5% with BMI > or =30 kg/m(2)). A minority of patients had a history of CVD (24.3%); of these, 11.7% had a history of myocardial infarction and most of the remainder had evidence of coronary artery disease. Subjects also had elevated blood pressure (BP) (predominantly systolic) (139.7/82.6 mm Hg), increased serum low-density lipoproteins cholesterol levels (3.27 mmol/L), and borderline elevation of triglyceride levels (1.97 mmol/L). Demographic data, BP, and lipid profiles in NAVIGATOR were similar to those of previous DM prevention trials, which were also based largely on meeting criteria for IGT. Medication use at baseline among NAVIGATOR subjects, which frequently included aspirin, beta-blockers, calcium channel blockers, diuretics, and lipid-lowering agents, reflects enhanced CVD risk. However, little prescribing of renin-angiotensin-aldosterone system blockers was observed, likely due to protocol exclusion criteria. In conclusion, the NAVIGATOR study comprises prediabetic subjects who typically have concurrent BP and metabolic disturbances and an enhanced risk of CVD, and are thus at higher risk for cardiovascular events than subjects in previous DM prevention trials.
 ...
PMID:Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. 2018 89

Chronic kidney disease (CKD) is a recognized risk multiplier for the development of cardiovascular disease (CVD), with CVD events representing the leading cause of morbidity and mortality in patients with CKD. The nature of CKD as a risk state relates both to the nature of CKD and the antecedent development of CVD. In addition, patients with CKD have increased rates of multiple conventional cardiac risk factors. Although early data regarding the relationship between CVD and CKD were limited because of the need for large data sets and multivariable analysis, the importance of recognizing this complex relationship is now clear. The essence of the relationship appears to be bidirectional, and therapy directed at improving natural history of chronic disease on one system generally improves prognosis in the other. Specifically, CVD outcomes have been shown to improve with the treatment of risk factors commonly found in association with CKD, including hypertension, diabetes, dyslipidemia, albuminuria, and smoking, as well as appropriate renin-angiotensin-aldosterone system blockade and antiplatelet therapy. Once hospitalized, management of acute coronary syndromes represents a key area of clinical investigation. The goal of this article is to highlight the importance of these topics in improving cardiovascular outcomes and use of appropriate treatment in CKD.
 ...
PMID:Cardiorenal interaction: appropriate treatment of cardiovascular risk factors to improve outcomes in chronic kidney disease. 2020 53

The prevalence of diabetes, hypertension, and cardiovascular disease (CVD) and chronic kidney disease (CKD) is increasing in concert with obesity. Insulin resistance, metabolic dyslipidemia, central obesity, albuminuria. and hypertension commonly cluster to comprise the cardiometabolic syndrome (CMS). Emerging evidence supports a shift in our understanding of the crucial role of elevated serum aldosterone in promoting insulin resistance and resistant hypertension. Aldosterone enhances tissue generation of oxygen free radicals and systemic inflammation. This increase in oxidative stress and inflammation, in turn, contributes to impaired insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. In this context, recent investigation indicates that hyperaldosteronism, which is often associated with obesity, contributes to impaired pancreatic beta-cell function as well as diminished skeletal muscle insulin metabolic signaling. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated, in part, by aldosterone's nongenomic as well as genomic signaling through the mineralocorticoid receptor (MR). In the CMS, there are increased circulating levels of glucocorticoids, which can also activate MR signaling in cardiovascular, adipose, skeletal muscle, neuronal, and liver tissue. Furthermore, there is increasing evidence that fat tissue produces a lipid soluble factor that stimulates aldosterone production from the adrenal zona glomerulosa. Recently, we have learned that MR blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation as well as reduces the progression of CVD and CKD. In summary, aldosterone excess exerts detrimental metabolic effects that contribute to the development of the CMS and resistant hypertension as well as CVD and CKD.
 ...
PMID:Aldosterone: role in the cardiometabolic syndrome and resistant hypertension. 2022 58

Insulinoresistance (IR) and endothelial dysfunction (ED) take part in forming cardiovascular complications. Hyperglycemia, dyslipidemia, and compensatory hyperinsulinemia are triggering factors in the development of ED in diabetes mellitus. Hyperactivation of the renin--angiotensin--aldosterone system and increasing influence of the sympathoadrenal system play an important role in the appearance of ED, which is characterized by a decrease in the synthesis of nitric oxide and an increase in the production of vasoconstrictors. At present, drugs used for ED correction only indirectly influence the functioning of endothelial cells. Eight pharmacological groups including more than 30 drugs are reviewed, which are capable of improving the endothelial function. Progress in the pharmacotherapy of ED stimulates the development of approaches to the individual choice of drugs and the directed correction of the functional state of vascular endothelium.
 ...
PMID:[Endothelial dysfunction in diabetes mellitus and possible ways of pharmacological correction]. 2036 1

Insulin resistance, dyslipidemia, hypertension, obesity, cardiovascular disease, and chronic kidney disease cluster together, and the incidence of all of these disease states is increasing throughout the world. Current strategies for hypertension management-including the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, and thiazide diuretics-are effective for most patients. However, as the incidence of hypertension increases in this target population, so does that of resistant hypertension. As such, significant research and effort must be put forth to bring blood pressure to goal and delay or prevent target organ damage. Such efforts should frequently include a dihydropyridine calcium channel blocker such as amlodipine. Other agents that are currently underused in this population for the treatment of resistant hypertension include nebivolol, carvedilol, aliskiren, and aldosterone antagonists. Finally, significant potential is seen for darusentan, an endothelin antagonist, if it comes to market.
 ...
PMID:Best strategies for hypertension management in type 2 diabetes and obesity. 2042 73

Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The effect of Mg deficiency in the development of insulin resistance in the rat model is well documented. Inflammation occurring during experimental Mg deficiency is the mechanism that induces hypertriglyceridemia and pro-atherogenic changes in lipoprotein metabolism. The presence of endothelial dysfunction and dyslipidemia triggers platelet aggregability, thus increasing the risk of thrombotic events. Oxidative stress contributes to the elevation of blood pressure. The inflammatory syndrome induces activation of several factors, which are dependent on cytosolic Ca activation. Recent findings support the hypothesis that the Mg effect on intracellular Ca2+ homeostasis may be a common link between stress, inflammation and a possible relationship to metabolic syndrome.
 ...
PMID:Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation. 2051 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>