Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
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Pregnancy is a metabolic and vascular 'stress test' for women and those who 'fail' are at increased risk of long-term cardiovascular complications. Specifically, women who develop preeclampsia (and/or other manifestations of placental dysfunction) are at increased risk of coronary heart disease, stroke and cardiovascular disease in general. The risk is highest among women who develop both maternal (e.g., hypertension and proteinuria) and fetal (e.g., intrauterine growth restriction) manifestations of abnormal placentation, especially with preterm delivery. Most women who develop a maternal placental syndrome return to a normal clinical state in the weeks following pregnancy and their absolute risk of cardiovascular disease in the short term is very low. However, perhaps having a placentally complicated pregnancy affords women the opportunity to personalize risk and take action. Action is needed. The fact that we, as a population, are getting heavier and more sedentary is an urgent public health issue. The American Heart Association recommends that all women (even those at low cardiovascular risk) pursue dietary and lifestyle changes, in addition to smoking cessation. Engaging women of child-bearing age who may be motivated by a complicated pregnancy would be very valuable, from a public health perspective, given the prevalence and importance of cardiovascular disease in women, and the central role of the woman as caregiver to children, spouses and other family members.
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PMID:Preeclampsia and future cardiovascular risk. 1733 72

Despite progress in recent years in the prevention, detection, and treatment of high blood pressure (BP), hypertension remains an important public health challenge. Hypertension affects approximately 1 billion individuals worldwide. High BP is associated with an increased risk of mortality and morbidity from stroke, coronary heart disease, congestive heart failure, and end-stage renal disease; it also has a negative impact on the quality of life. Hypertension cannot be eliminated because there are no vaccines to prevent the development of hypertension, but, its incidence can be decreased by reducing the risk factors for its development, which include obesity, high dietary intake of fat and sodium and low intake of potassium, physical inactivity, smoking, and excessive alcohol intake. For established hypertension, efforts are to be directed to control BP by lifestyle modification (LSM). However, if BP cannot be adequately controlled with LSM, then pharmacotherapy can be instituted along with LSM. Normalization of BP reduces cardiovascular risk (for cardiovascular death, myocardial infarction, and cardiac arrest), provides renoprotection (prevention of the onset or slowing of proteinuria and progression of renal dysfunction to end-stage renal disease in patients with hypertension, diabetes mellitus types 1 and 2, and chronic renal disease), and decreases the risk of cerebrovascular events (stroke and cognition impairment), as has been amply demonstrated by a large number of randomized clinical trials. In spite of the availability of more than 75 antihypertensive agents in 9 classes, BP control in the general population is at best inadequate. Therefore, antihypertensive therapy in the future or near future should be directed toward improving BP control in treated hypertensive patients with the available drugs by using the right combinations at optimum doses, individually tailored gene-polymorphism directed therapy, or development of new modalities such as gene therapy and vaccines. Several studies have shown that BP can be reduced by lifestyle/behavior modification. Although, the reductions appear to be trivial, even small reductions in systolic BP (for example, 3-5 mm Hg) produce dramatic reduction in adverse cardiac events and stroke. On the basis of the results of clinical and clinical/observational studies, it has been recommended that more emphasis be placed on lifestyle/behavior modification (obesity, high dietary intake of fat and sodium, physical inactivity, smoking, excessive alcohol intake, low dietary potassium intake) to control BP and also to improve the efficacy of pharmacologic treatment of high BP. New classes of antihypertensive drugs and new compounds in the established drug classes are likely to widen the armamentarium available to combat hypertension. These include the aldosterone receptor blockers, vasodilator beta-blockers, renin inhibitors, endothelin receptor antagonists, and dual endopeptidase inhibitors. The use of fixed-dose combination drug therapy is likely to increase. There is a conceptual possibility that gene therapy may yield long-lasting antihypertensive effects by influencing the genes associated with hypertension. But, the treatment of human essential hypertension requires sustained over-expression of genes. Some of the challenging tasks for successful gene therapy that need to be mastered include identification of target genes, ideal gene transfer vector, precise delivery of genes into the required site (target), efficient transfer of genes into the cells of the target, and prompt assessment of gene expression over time. Targeting the RAS by antisense gene therapy appears to be a viable strategy for the long-term control of hypertension. Several problems that are encountered in the delivery of gene therapy include 1) low efficiency for gene transfer into vascular cells; 2) a lack of selectivity; 3) problem in determining how to prolong and control transgene expression or antisense inhibition; and 4) difficulty in minimizing the adverse effects of viral or nonviral vectors. In spite of the hurdles that face gene therapy administration in humans, studies in animals indicate that gene therapy may be feasible in treating human hypertension, albeit not in the near future. DNA testing for genetic polymorphism and determining the genotype of a patient may predict response to a certain class of antihypertensive agent and thus optimize therapy in individual patients. In this regard, there are some studies that report the effectiveness of antihypertensive therapy based upon the genotype of selected patients. Treatment of human hypertension with vaccines is feasible but is not likely to be available in the near future.
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PMID:The future of antihypertensive treatment. 1741 79

Apolipoprotein (apo) B48 is a structural protein of chylomicrons. Fasting serum levels of apoB48 suggest the presence of small number of remnant chylomicron particles which are thought to be an atherogenic lipoprotein. In view of the high incidence of coronary heart disease (CHD) in patients with diabetic nephropathy, we decided to measure the plasma apoB48 level in type 2 diabetics with diabetic nephropathy at various stages to ascertain how apoB48 relates to the progression of diabetic nephropathy. Patients with type 2 diabetes (n=105) were stratified into four groups: normo-albuminuria, micro-albuminuria, overt-proteinuria, and patients with end-stage renal disease (ESRD) receiving hemodialysis. Age-matched-diabetic hypertensive patients (n=24) and non-diabetic ESRD patients on hemodialysis (n=47) were also enrolled. Plasma triglyceride (TG) levels rose as diabetic nephropathy progressed to overt-proteinuria. No further elevation in TG was observed in diabetic ESRD, however, and the TG levels were normal in non-diabetic ESRD. A similar pattern was observed for remnant-like particle-cholesterol (RLP-C). In contrast to the changes observed for TG and RLP-C, the levels of apoB48 increased steadily as the diabetic nephropathy progressed (control, 3.7; normo, 5.7; micro, 6.9; overt, 10.6 mg/l, respectively). ApoB48 peaked in the diabetic ESRD (19 mg/l) and was also markedly elevated in non-diabetic ESRD (10.1mg/l). The apoB48/TG and apoB48/total-apoB ratios were substantially elevated in both diabetic and non-diabetic ESRD. These results are the first to demonstrate remarkable elevations of plasma apoB48 in patients with both diabetic and non-diabetic ESRD. The remarkably high level of apoB48 in diabetic ESRD seems to be attributable to dyslipidemia induced by both diabetic nephropathy and ESRD.
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PMID:Remarkable increase of apolipoprotein B48 level in diabetic patients with end-stage renal disease. 1746 54

In a large randomized trial of statin therapy in patients of South-Asian origin with hypercholesterolemia, 740 patients in the United States and Canada received 6 weeks of treatment with rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg. A total of 485 patients (66%) were categorized as being at high risk of coronary heart disease and had a National Cholesterol Education Program Adult Treatment Panel III treatment goal of low-density lipoprotein (LDL) cholesterol <100 mg/dl (<2.6 mmol/L). LDL cholesterol decreased by 45% with rosuvastatin 10 mg versus 40% with atorvastatin 10 mg (p = 0.0023) and by 50% with rosuvastatin 20 mg versus 47% with atorvastatin 20 mg (p = NS). National Cholesterol Education Program Adult Treatment Panel III LDL cholesterol goal achievement rates in high-risk patients (all patients) were 76% (79%) and 88% (89%) with rosuvastatin 10 and 20 mg, respectively, compared with 70% (76%) and 81% (85%) with atorvastatin 10 and 20 mg, respectively. Rosuvastatin and atorvastatin were well tolerated. There were no clinically relevant differences between statins in adverse events or incidence of creatine kinase >10 times the upper limit of normal, alanine aminotransferase >3 times the upper limit of normal on 2 consecutive occasions, or proteinuria or hematuria over the relatively short duration of treatment. In conclusion, statin therapy was well tolerated and effective in decreasing LDL cholesterol in patients of South-Asian origin, with the 10- and 20-mg doses of rosuvastatin and atorvastatin allowing most patients to reach recommended LDL cholesterol goals.
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PMID:Comparison of rosuvastatin versus atorvastatin in South-Asian patients at risk of coronary heart disease (from the IRIS Trial). 1753 77

Ankle brachial pressure index (ABPI) is a non-invasive marker of atherosclerosis, helpful to identify subjects at high-risk for coronary heart disease (CHD) among large populations with cardiovascular disease (CVD) risk factors. The diagnostic role of ABPI has been also recognized in patients with diabetes. In the present study, the role of an ABPI score < 0.90 in predicting CHD has been evaluated in a large series of patients with Type 2 diabetes mellitus and compared to other known CVD risk factors. Nine hundred and sixty-nine (mean age was 66.1 yr) consecutive patients with Type 2 diabetes mellitus were evaluated. The patients were followed-up for 18.3+/-5.2 months (range 12- 24) and all events of CHD, defined as myocardial infarction, unstable and resting angina or coronary atherosclerosis at the instrumental investigation (at the coronary angiography and/or perfusion stress testing) were recorded. A rate of 17.5% of CHD events were recorded in diabetic population during the follow-up period. The relative risk of CHD was significantly increased for male patients [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.1-2.2], patients with age > or = 66 yr (OR: 1.8; 95% CI: 1.3-2.5), body mass index (BMI) > 30 (OR: 1.5; 95% CI: 1.1-2.1), waist circumference > 88 cm for females and 102 cm for males (OR: 1.5; 95% CI: 1.0-2.1), proteinuria > or = 30 microg per min (OR: 1.6; 95% CI: 1.1-2.3), LDL-cholesterol > or = 100 mg/dl (OR: 2.1; 95% CI: 1.5-3.0), glycated hemoglobin > 7% (OR: 1.6; 95% CI: 1.1-2.3), insulin therapy (OR: 1.9; 95% CI: 1.3-2.9), and ABPI < 0.90 (OR: 3.7; 95% CI: 2.2- 6.2). BMI was higher in patients with ABPI < 0.90 than in those with ABPI > or = 0.90 (p<0.05). At the multivariate analysis, ABPI < 0.90 was the best factor independently associated with CHD (p<0.001). APBI < 0.90 is strongly associated to CHD in Type 2 diabetic patients. We recommend to use ABPI in diabetic patients and to carefully monitor diabetic subjects with an ABPI lower than 0.90.
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PMID:Ankle brachial pressure index usefulness as predictor factor for coronary heart disease in diabetic patients. 1799 62

Abnormal glucose metabolism (AGM) is common but underestimated in patients with coronary heart disease (CHD). Here, we reported 898 in-hospital patients with primary hypertension (PH) at the university hospitals in developed regions of China. Oral glucose tolerance test (OGTT) was performed in those without known type-2 diabetes mellitus (2-DM). A total of 158 patients had known 2-DM and 32 were newly diagnosed as 2-DM by fasting blood glucose (FBG). OGTT revealed that 83 had 2-DM and 296 had impaired glucose tolerance (IGT). The proportion of 2-DM and AGM increased from 21.2 to 30.4% and from 57.5 to 68.7% upon OGTT. Prevalence of AGM and 2-DM increased with the increase of age, and incidence of AGM and 2-DM was significant higher in patients with risk factors (including CHD, overweight, hyperlipidaemia, proteinuria) than those without risk factors mentioned above. Glucose was not sufficiently controlled in 55.1% of the patients with 2-DM upon treatment, well controlled in 35.4% and not controlled in 9.5%. So AGM is also prevalent in PH patients especially the elders and those with risk factors, which was underestimated in most cases. Moreover, much lower awareness, treatment and control of 2-DM occurred in some regions of China, thus strengthening health education for patients and heightening consciousness of doctor are very important and eminent. Except for FBG, more attention should be paid to postprandial blood glucose ignored before, and OGTT should be a routine procedure in PH patients, especially in older patients and those with the factors mentioned above.
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PMID:Glucometabolic state of in-hospital patients with primary hypertension in sub-population of partial regions in China. 1820 32

Depending on the reduction in glomerular filtration rate (GFR) as a measure of renal insufficiency and depending on their age, patients with chronic kidney disease have a 1.5 to 1,000-fold higher cardiovascular risk. Renal insufficiency is inherently an independent risk factor for cardiovascular events, which is likewise the case for patients also presenting with hypertension or diabetes mellitus. When cardiac insufficiency or coronary heart disease is already manifest, the GFR is the most important predictive factor for the patients' further survival. Proteinuria or albuminuria as signs of kidney disease are also important markers and correlate with the cardiovascular risk in the range of both macro- and microalbuminuria. Endothelial dysfunction, oxidative stress, dyslipidemia, and increased atherosclerosis are being discussed as pathophysiological mechanisms of elevated cardiovascular risk.
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PMID:[Chronic kidney disease and the cardiovascular system]. 1830 69

Diabetes mellitus often develops in patients with hypertension. We investigated predictors of diabetes mellitus development in hypertensives at risk of developing the disease in the VALUE trial population. Among the 9995 non-diabetic hypertensive patients at baseline, 1298 patients developed diabetes mellitus during the average follow-up of 4.2 years. New-onset diabetes mellitus was defined from adverse event reports, information about new antidiabetic medication and/or a fasting glucose >or=7.0 mmol l(-1) at the end of trial. Twenty-five potential baseline predictors of new-onset diabetes mellitus were analysed by univariate logistic regression and 14 of 25 predictors were found to be statistically significant with a P-value <0.05. The predictors were in order of decreasing significance; glucose, body mass index (BMI), age, uric acid, non-Caucasian race, haemoglobin, heart rate, randomized study treatment, history of coronary heart disease (CHD), gender, total cholesterol, proteinuria, potassium and creatinine. Multivariate stepwise logistic regression analyses were used and potential baseline predictors of new-onset diabetes mellitus were considered significant by four different models (P-value <0.001). The final multivariate model selected included all patients, but not treatment group as a potential predictor, and the six significant predictors identified from this model were glucose, BMI, non-Caucasian race, age, heart rate and history of CHD. In conclusion, glucose and BMI were the most important predictors of new-onset diabetes mellitus in hypertensive patients at high cardiovascular risk, and easily accessible clinical characteristics strongly predict patients at risk of developing diabetes mellitus.
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PMID:Predictors of new-onset diabetes mellitus in hypertensive patients: the VALUE trial. 1849 56

Metabolic syndrome (MS) encompasses a series of diseases which, when combined, increase vascular risk more than the sum of their individual risks. Insulin resistance (IR) is one of the basic components of MS. - Abdominal fat distribution is an IR marker and is associated to factors increasing vascular risk such as dyslipidemia, high blood pressure, and hyperglycemia, components of the so-called metabolic syndrome. - IR is related to glomerular sclerosis and renal failure through several mechanisms, Including genetic and environmental factors, and stimulation of the renin-angiotensin-aldosterone system. - IR usually precedes development of DM, and therefore contributes to its early identification. MS increases the risk of chronic complications from DM and is associated to an increased prevalence of cardiovascular disease, particularly coronary heart disease, increasing mortality from this cause. - The presence of MS in DM2 is usually associated to a greater prevalence of microalbuminuria or proteinuria and peripheral polyneuropathy.
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PMID:[Metabolic syndrome and kidney disease]. 1901 36

The diabetes epidemic continues to grow unabated, with a staggering toll in micro- and macrovascular complications, disability, and death. Diabetes causes a two- to fourfold increase in the risk of cardiovascular disease, and represents the first cause of dialysis treatment both in the UK and the US. Concomitant hypertension doubles total mortality and stroke risk, triples the risk of coronary heart disease and significantly hastens the progression of microvascular complications, including diabetic nephropathy. Therefore, blood pressure reduction is of particular importance in preventing cardiovascular and renal outcomes. Successful antihypertensive treatment will often require a combination therapy, either with separate drugs or with fixed-dose combinations. Angiotensin converting enzyme (ACE) inhibitor plus diuretic combination therapy improves blood pressure control, counterbalances renin-angiotensin system activation due to diuretic therapy and reduces the risk of electrolyte alterations, obtaining at the same time synergistic antiproteinuric effects. ACE inhibitor plus calcium channel blocker provides a significant additive effect on blood pressure reduction, may have favorable metabolic effects and synergistically reduce proteinuria and the rate of decline in glomerular filtration rate, as evidenced by the GUARD trial. Finally, the recently published ACCOMPLISH trial showed that an ACE inhibitor/calcium channel blocker combination may be particularly useful in reducing cardiovascular outcomes in high-risk patients. The present review will focus on different ACE inhibitor combinations in the treatment of patients with type 2 diabetes mellitus and hypertension, in the light of recent clinical trials, including GUARD and ACCOMPLISH.
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PMID:Choice of ACE inhibitor combinations in hypertensive patients with type 2 diabetes: update after recent clinical trials. 1947 78


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