Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main complications of hypertension, i.e. coronary heart disease, ischaemic strokes and peripheral vascular disease (PVD), are usually related to thrombosis. Increasing evidence also suggests that hypertension fulfils the components of Virchow's triad, thus conferring a prothrombotic or hypercoagulable state, as evident by abnormalities of haemostasis, platelets and endothelial function. It therefore seems plausible that use of antithrombotic therapy may help prevent these thrombosis-related complications of hypertension. Indeed, hypertensive patients with an estimated 10-year CHD risk > or = 15% will have their cardiovascular risk reduced by 25% using antihypertensive treatment, but the addition of aspirin further reduces major cardiovascular events by 15%. Recent guidelines recommend the use of aspirin 75 mg daily for hypertensive patients who have no contraindication to aspirin, in one of the following categories: (i) secondary prevention - cardiovascular complications (myocardial infarction, angina, non-haemorrhagic stroke, peripheral vascular disease or atherosclerotic renovascular disease); and (ii) primary prevention - those with blood pressure controlled to < 150/90 mmHg and one of: (a) age > or = 50 years and target organ damage (e.g. LVH, renal impairment, or proteinuria); (b) a 10-year CHD risk > or = 15%; or (c) type II diabetes mellitus. However, some of the risks of aspirin administration, namely increased incidence of major bleeding events, may possibly outweigh the benefits, especially in low-risk individuals.
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PMID:Should patients with hypertension receive antithrombotic therapy? 1128 41

The co-existence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Overwhelming evidence supports aggressive treatment of hypertension in diabetic patients. However, only a small percentage of diabetic hypertensive patients reach their treatment goal of blood pressure (BP) < 130/80 mmHg. Tight BP control is not only cost-effective but also more rewarding than glycaemic control. The optimal goal of BP control in diabetics should be 130/80 mmHg. In subjects with diabetes and renal insufficiency, the BP should be lowered to 125/75 mmHg to delay the progression of renal failure. The choice of an antihypertensive agent should be based on proven effects on morbidity and mortality rather than on surrogate parameters such as lipid or glucose. Limited data suggests that an angiotensin converting enzyme inhibitor (ACEI) is the agent of choice, especially in those with proteinuria or renal insufficiency. beta-blockers (betaBs) can be the first-line agent in diabetics with coronary heart disease, while thiazide diuretics (TD) and calcium-channel blockers (CCBs) are the second-line drugs. Angiotensin II-receptor blockers (ARBs) may be proven to be as effective as ACEIs in diabetics with hypertension. alpha-adrenergic antagonists (AAAs) should be avoided. Most hypertensive patients require more than one agent to control their BP. There is no evidence to support one combination regimen over others; nevertheless, a combination of an ACEI with a TD or a betaB may be the most cost-effective regimens compared to other combinations.
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PMID:Pharmacotherapy of hypertension in patients with diabetes mellitus. 1182 18

The hyperglycemic milieu in diabetes results in the formation of advanced glycation end products (AGEs) that predominantly act through specific receptors, particularly the receptor for AGEs (RAGE). Two functional polymorphisms in the promoter of the RAGE gene (-429 T/C and -374 T/A) and one in the AGE binding domain in exon 3 (G82S) were studied in 996 Finnish type 1 diabetic patients. In patients with poor metabolic control (HbA(1c) >9.5%), the AA genotype of the -374 T/A polymorphism was more common in those with a normal albumin excretion rate than in those with proteinuria (30 vs. 10%, P = 0.01). We observed less coronary heart disease (6 vs. 14%, P < 0.05), acute myocardial infarction (2 vs. 14%, P = 0.01), and peripheral vascular disease (2 vs. 14%, P < 0.05) in patients with the AA genotype of the -374 T/A polymorphism than in those with the TT + TA genotype. Thus, the association between the RAGE -374 T/A homozygous AA genotype and cardiovascular disease as well as albumin excretion in type 1 diabetic patients with poor metabolic control suggests a gene-environment interaction in the development of diabetic nephropathy and cardiovascular complications.
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PMID:The functional -374 T/A RAGE gene polymorphism is associated with proteinuria and cardiovascular disease in type 1 diabetic patients. 1260 36

There appear to be ethnic disparities in frequencies of diabetic complications in type 2 diabetic patients and such data from Asian countries are relatively few and limited. Thai type 2 diabetic patients who attended the diabetic clinic at Prince of Songkla University hospital during January-December 1997 and had no history of coronary heart disease (CHD) and stroke were studied to determine cause of death and to establish the incidence of and risk factors for cardiovascular disease (CVD). All patients were followed to death or to the end of year 2001. End-points included death from any cause, fatal and nonfatal CHD, fatal and nonfatal stroke and lower-extremity amputation. There were 229 patients who were followed for 4.2+/0.7 (S.D.) years (range: 0.6-5.0) with total follow-up period 958.2 patient-years. Twenty-nine patients died during follow-up; the total mortality rate was 30.3 (95%CI 20.2-43.4)/1000 patient-years. Of these, 9(9.4/1000 patient-years; 95%CI 4.3-17.8) died from sepsis, 7(7.3/1000 patient-years; 95%CI 2.9-15.0) from CVD, 5(5.2/1000 patient-years; 95%CI 2.7-12.2) from end-stage renal disease, 3(3.1/1000 patient-years; 95%CI 0.6-9.2) from malignancy and 1(1.0/1000 patient-years; 95%CI 0.03-5.8) from peripheral vascular disease. The incidences of fatal and nonfatal CHD as well as fatal and nonfatal stroke were 21.4(95%CI 13.0-33.0)/1000 and 12.8(95%CI 6.6-22.4)/1000 patient-years, respectively whereas the incidence of lower-extremity amputation was 4.3(95%CI 1.2-10.9)/1000 patient-years. Age, the presence of proteinuria and serum HDL-C < or = 0.9 mmol/l were independent risk factors of CHD with the respective Hazard ratios 1.09(95%CI: 1.02-1.17; P=0.016), 4.41(95%CI: 1.18-16.45; P=0.027) and 3.91(95%CI: 1.20-12.80; P=0.024). In conclusion, sepsis and CVD were the major causes of death accounting for approximately 50% of total mortality in Thai type 2 diabetic patients. Age, the presence of proteinuria and low HDL-C were independent risk factors for the development of CHD. The mortality from and the incidence of CHD in Thai type 2 diabetic patients are lower than those reported from Caucasian populations but the incidence of stroke appears to be higher. These findings need to be confirmed by a large-scale population-based study.
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PMID:Causes of death, incidence and risk factors of cardiovascular diseases in Thai type 2 diabetic patients: a 5 year follow-up study. 1282 63

Cardiovascular diseases (CVD) have become the leading cause of mortality in renal transplant recipients. Well-known cardiovascular (CV) risk factors and graft dysfunction both play an important role in the development of the posttransplantation CV events. We studied 233 stable kidney transplant patients to establish the prevalence of CVD and to assess CV risk factors that can be evaluated (and modified) in daily clinical practice. While 6.2% of the patients had coronary heart disease (CHD) before the transplantation, 16% displayed at least 1 CV event posttransplantation. The most significant factors associated with CV events were as follows: gender, length of smoking, diabetes mellitus, hepatitis C virus antibodies (HCV), dyslipidemia, proteinuria, and serum creatinine levels.
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PMID:Risk factors for cardiovascular disease after renal transplantation. 1296 71

In the individual patient, the goal of antihypertensive treatment is to lower the blood pressure (BP) to a level that minimizes the patient's risk of cardiovascular complications. However, most of our knowledge regarding what this level of BP should be is derived from population studies and large clinical trials. Population studies have shown that elevated BP is associated with an increased risk of morbidity and mortality from coronary heart disease, stroke, heart failure, and renal failure. Cardiovascular risk begins to increase when BP exceeds 115/75 mm Hg and doubles with each increment of 20 mm Hg in systolic BP and 10 mm Hg in diastolic BP.The clinical benefit of BP reduction in patients with hypertension is well established. Thus, patients with less severe elevations in BP (high-normal) are at increased risk. Patients with diabetes or proteinuria benefit from even more aggressive reductions in BP. Despite the well-established benefits of BP reduction, hypertension is still not well treated, underscoring the need for more aggressive detection and better management. Although data from large clinical trials have provided valuable information to help guide treatment, application of clinical trial results to individual patients is limited by the heterogeneity of patient populations with respect to patient risk, comorbidities, and differences in genetic and environmental background. Ultimately, the treatment decisions should be tailored to each patient, integrating as much information as possible concerning the patient's history, risk, pathophysiology, and lifestyle.
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PMID:Examining therapeutic goals: population versus individual-based approaches. 1462 57

In the United States, 50 million Americans are estimated to have hypertension. Over the past several decades, it has become clear that hypertension is both a cause and a consequence of kidney disease. In contrast to the striking decline in mortality rates from both stroke and coronary heart disease, the prevalence of hypertension as a cause of end-stage renal disease (ESRD) has increased such that it is now the second most common cause of ESRD in the United States. Hypertension and proteinuria occur in most patients with chronic kidney disease and are risk factors for faster progression of kidney disease. Antihypertensive agents reduce blood pressure and urine protein excretion and slow the progression of kidney disease. The level of blood pressure achieved and use of renin-angiotensin-aldosterone system-blocking agents is critical for delaying progression of renal disease in all ethnic groups.
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PMID:Antihypertensive drugs and the kidney. 1548 98

Drugs that inhibit the renin-angiotensin system (RAS), namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor antagonists (ARA) are gaining increasing popularity as initial medications for the management of hypertensive patients. In the year 2002, ACE-I were the most commonly prescribed drugs for the treatment of hypertension in USA. Although their antihypertensive efficacy as monotherapy is similar to other antihypertensive agents, they have the advantage of better tolerability, limited side effects and a favorable metabolic profile. When compared to other antihypertensive agents (diuretics, beta-adrenergic blockers and calcium antagonists) in large clinical trials, ACE-I and ARA provided no additional advantages regarding improvement in cardiovascular and total mortality. With the exception of the superiority of ARA in prevention of stroke, RAS inhibitors have no advantage over other agents in prevention of other cardiovascular morbid events, namely, heart failure (though ACE-I are superior to calcium antagonists), coronary heart disease and total cardiovascular events. However, there is the possibility that these agents have other benefits beyond blood pressure lowering. At equal degrees of blood pressure reduction, RAS inhibitors prevent or delay the development of diabetes mellitus and provide better end-organ protection, kidneys, blood vessels and the heart when compared with other antihypertensive agents. The combined use of ACE-I and ARA is particularly useful in organ protection. RAS inhibitors are specifically indicated in the treatment of hypertension in patients with impaired left ventricular systolic function, diabetes, proteinuria, impaired kidney function, myocardial infarction, multiple cardiovascular risk factors and possibly elderly patients. The main limitation of the ACE-I is cough and rarely angioedema. Elderly patients or those who are volume depleted or receiving large doses of diuretics or in heart failure are liable to develop hypotensive reaction and/or deterioration in kidney function.
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PMID:RAS inhibition in hypertension. 1639 19

Proteinuria, high serum creatinine, and reduced glomerular filtration rate (GFR) have been associated with increased mortality from cardiovascular disease (CVD) and all causes. However, the combined effect of proteinuria with serum creatinine and GFR on CVD or all-cause mortality has not been well investigated. We conducted a 10-year prospective cohort study of 30,764 men and 60,668 women aged 40-79 years who participated in annual health checkups in 1993. The Cox proportional hazards model was used to estimate the relative risk (RR) after adjusting for age, smoking, and other cardiovascular risk factors. The multivariable RR (95% confidence interval (CI)) of CVD death for positive vs negative proteinuria was 1.38 (1.05-1.79) among men and 2.15 (1.64-2.81) among women. The respective RR for the highest vs lowest creatinine groups (> or = 1.3 vs < or = 0.8 mg/dl for men and > or = 1.1 vs < or = 0.6 mg/dl for women) was 1.56 (1.19-2.04) among men and 2.15 (1.58-2.93) among women. The respective RR for GFR < 60 vs > r = 100 ml/min/1.73 m2 was 1.65 (1.25-2.18) among men and 1.81 (1.39-2.36) among women. For individuals with proteinuria combined by hypercreatininemia or reduced GFR, the risk of CVD death was two-fold higher in men and 4-6-fold higher in women compared to those without proteinuria and with normal creatinine level or GFR. Similar associations were observed for stroke, coronary heart disease, and all-cause mortality. Proteinuria, and hypercreatininemia or reduced GFR and their combination were significant predictors of CVD and all-cause mortality.
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PMID:The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. 1650 89

Increased coronary heart disease risk in HIV-positive patients using antiretroviral therapy (ART) has been a controversial topic since 1998 when the dyslipidaemic effect of protease inhibitors (PIs) was recognised. Accumulating evidence suggests an association between ART and increased coronary heart disease risk. In 2003, the large, prospective D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study reported a 26% relative increase in the rate of myocardial infarction per year of exposure during the first 4-6 years of use. As the HIV-population grows older, infectious disease specialists have to consider unfamiliar areas of internal medicine such as lipid-lowering therapy and smoking cessation. Moreover, the ART regimen itself may be a modifiable risk factor, as there are both class differences and within-class differences in the tendency to increase lipids. Most nucleoside reverse transcriptase inhibitors (NRTIs), including the newer agents tenofovir disoproxil fumarate and emtricitabine, have little or no effect on lipid levels or glucose metabolism. One exception is the highly effective NRTI stavudine, which has a dyslipidaemic profile and a negative effect on glucose metabolism. In contrast the non-nucleoside reverse transcriptase inhibitor nevirapine may increase the 'good cholesterol' high-density lipoprotein (HDL) cholesterol and thus reduce the total cholesterol : HDL cholesterol index. Most of the PIs have some dyslipidaemic effect, especially ritonavir (alone or in combination with other PIs), fosamprenavir and the novel PI tipranavir. Only atazanavir, and to some extent saquinavir, seem to have little effect on lipid levels and glucose metabolism. Studies on blood pressure in HIV-positive patients have been contradictory. Apart from a recent report from the D:A:D study where lower blood pressure was found in patients receiving NNRTIs, the influence of the individual drugs on blood pressure is unknown. When hypertension is detected in a HIV-positive patient, creatinine clearance (CL(CR)) should be calculated and the urine checked for proteinuria. When CL(CR) is <30 mL/min, tenofovir disoproxil fumarate is not recommended. Many hypertensive HIV-positive patients have proteinuria and an ACE inhibitor or an angiotensin II receptor antagonist is a better choice than a thiazide diuretic or calcium channel antagonist in these patients. In addition, physicians treating patients with ART should be especially aware of the long list of possible interactions between PIs and anti-hypertensive- and lipid-lowering drugs. This review discusses important clinical aspects of treating middle-aged HIV-positive patients who have an increased risk of experiencing a cardiovascular event.
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PMID:Cardiovascular risk in patients with HIV Infection: impact of antiretroviral therapy. 1710 Apr 7


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