Antihypertensive Drugs In Hypertensive Patients Research Articles

Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive patients with albuminuria

Although inhibitors of the renin-angiotensin system are effective as first-line antihypertensive drugs in hypertensive patients with chronic kidney disease, they cannot completely prevent the progression of renal injury. Many animal studies, including our own, and a few human studies suggest that mineralocorticoid receptor blockade could inhibit the ongoing renal damage in chronic kidney disease. Thus, we designed this double-blinded, randomized, placebo-controlled trial to evaluate the antialbuminuric effect of a low dose (50 mg day(-1)) of the mineralocorticoid receptor antagonist eplerenone. The study subjects will include 340 hypertensive patients (blood pressure: 130-180/80-100 mm Hg) with albuminuria (urinary albumin/creatinine ratio: 30-600 mg g(-1) in the first morning void urine), who are treated with an inhibitor of the renin-angiotensin system. Other classes of antihypertensive drugs may be added as needed to achieve the target blood pressure (<130/80 mm Hg). The primary study end point is the change in the urinary albumin/creatinine ratio after a 1-year study period. This trial is expected to show whether a low dose of mineralocorticoid receptor antagonists can exert an antialbuminuric effect in patients with chronic kidney disease.

Change of Selection to Antihypertensive Drugs in Hypertensive Patients with Diabetes Mellitus: In Pohang · Gyeongju Primary Care Research Network

Background: Angiotensin converting enzyme inhibitors (ACEIs) or Angiotensin II type 1 receptor blockers (ARBs) are drugs for hypertensive patients with diabetes mellitus. But prescription rate in 2005 year study of Pohang · Gyeongju area was only 30.8%. Therefore, a study on the change of prescription rate in the same area after 3 years was done. Methods: During three months from January 2008, 152 hypertensive patients with diabetes mellitus on their prescribed antihypertensive medications by 9 family physicians in visiting order were analyzed. After the analysis, the infl uencing factors for such prescriptions were ascertained by directly visiting each physicians who prescribed them. Results: A regimen of 16 antihypertensive agents were prescribed by these family physicians. Prescription count of ACEIs or ARBs was 101 cases (66.4%). ACEIs single therapy was 19 cases (12.5%), ACEIs combination therapy was 7 cases (4.6%), ARBs single therapy was 31 cases (20.4%) and ARBs combination therapy was 44 cases (28.9%). The ACEIs or ARBs which were selected by physicians that followed compelling indication was 5 (55.6%), reduce pressure effect was 3 (33.3%) and public relations of new medicine was 1 (11.1%). Conclusion: In prescribing antihypertensive agents for patients with diabetes mellitus, selection of ACEIs or ARBs was increased from 30.8% to 66.4%. Education of recommended standard by participating in such study and developing of excellent new medicines may increase such change.

Novel sandwich ELISA for human angiotensinogen

We recently reported that urinary excretion rates of angiotensinogen (U(AGT)) provide a specific index of intrarenal renin-angiotensin (ANG) system (RAS) status in ANG II-dependent hypertensive rats. When this is shown to be applicable to human subjects, a diagnostic test to identify those hypertensive patients most likely to respond to an RAS blockade could provide useful information to allow a mechanistic rationale for selection of an optimized approach to treatment of hypertensive patients. However, simple and accurate methods to measure human angiotensinogen (hAGT) are unavailable. For future studies of human subjects, we developed antibodies and a sensitive and specific quantification system for hAGT using a sandwich ELISA. We raised two antibodies against hAGT: a mouse monoclonal antibody and a rabbit polyclonal antibody. The standard curve of this ELISA exhibited a high linearity (0.31-20 ng/ml). The correlation coefficient was >0.99. Plasma angiotensinogen concentrations of healthy volunteers ranged from 28 to 71 microg/ml (n = 10). The ratio of U(AGT) to urinary creatinine concentration ranged from 5.0 to 30 microg/g (n = 7). Intra- and interassay coefficients of variation ranged from 4.4 to 5.5% and from 4.3 to 7.0%, respectively. This ELISA system had no cross-reactivity with major proteins in proteinuric urine samples, such as human albumin, immunoglobulin, or transferrin. Moreover, the cross-reactivity of the system with angiotensin peptides was also negligible. This hAGT ELISA will be a useful tool to investigate the relationship of U(AGT) and reactivity to antihypertensive drugs in hypertensive patients.

Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan

The importance of tight blood pressure (BP) control has been established. We performed cross-sectional studies on the current status of BP control and the prescription and efficacy of antihypertensive drugs in hypertensive patients in Japan. The data were also evaluated in subgroups with or without diabetes mellitus (DM) and in winter and summer. Analyses were performed on the collected data of 12,437 treated hypertensive patients in winter and 5,972 in summer 2002. In winter, 50.3% of patients received calcium channel blockers (CCBs), 15.3% received angiotensin converting enzyme inhibitors (ACEIs) and 11.0% received angiotensin receptor blockers (ARBs). In the patients receiving monotherapy, 69% of patients received a CCB, 13% an ACEI and 11.0% an ARB. A total of 2,918 patients received combination therapy, and CCBs were the most frequently (89.6%) prescribed component of such therapy. Prescriptions of beta-blockers (BBs) decreased and those of CCBs and diuretics (D) increased with age (p<0.001). The rate of patients with adequately controlled BP less than 140/90 mmHg was 40.3% in the CCB group, 37.6% in the D group, and 36.9% in the BB group (p<0.001). In patients receiving combination therapy, those with CCB+D had the best rate of BP control (40.7%). The rate of patients with adequately controlled BP was lower in winter than in summer at both a target BP of 140/90 mmHg (36.2% vs. 43.8%, p<0.001) and a target BP of 130/85 mmHg in patients younger than 60 years old (15.5% vs. 18.6%, p<0.02). In diabetic patients, the target BP (130/80 mmHg) was achieved in only 11.3%, which was lower (p<0.05) than the rate in non-diabetic patients (13.1%). In conclusion, the present cross-sectional study showed that CCBs were the most frequently prescribed agent for the treatment of hypertension in Japan. The rate of adequate BP control was less than 50% and was even worse in patients with DM and in winter. Our results indicate that physicians should treat hypertension more intensively to achieve the target BP.

Evaluation of Different Combination of Antihypertensive Drugs in Hypertensive Patients Not Adequately Controlled by Previous Monotherapy

Evaluation of Different Combination of Antihypertensive Drugs in Hypertensive Patients Not Adequately Controlled by Previous Monotherapy

Microalbuminuria in essential hypertension and diabetes mellitus.

Microalbuminuria is defined as abnormally elevated urinary albumin excretion below the level of clinical albuminuria (albustix). This represents a urinary albumin excretion rate of 20-200 micrograms/min, equal to 30-300 mg/24 h. Urinary albumin excretion can vary as much as 40% with natural fluctuations, and so several tests should be done. Inexpensive radioimmunoassay, enzyme-linked immunosorbent assays or immunoturbidimetric assays are now routine in many clinical laboratories. The prevalence of microalbuminuria in essential hypertension and diabetes is about the same: 25% (range 14-31) and 20% (9-27), respectively. Increased transglomerular passage is the major mechanism of microalbuminuria in both the above-mentioned conditions; increased hydraulic glomerular capillary pressure and glomerular lesions probably both contribute. Microalbuminuria is highly predictive of the development of diabetic nephropathy but the predictive power in relation to hypertensive nephropathy remains to be established. However, in both conditions microalbuminuria is associated with an increased risk of retinopathy, left ventricular hypertrophy, fatal and non-fatal cardiovascular disease and all-cause mortality. The following mechanisms have been suggested as a link between microalbuminuria and these findings: endothelial dysfunction, insulin resistance, hyperinsulinemia, dyslipoproteinemia and a procoagulant state. Blood pressure lowering reduces microalbuminuria in essential hypertension and in diabetes mellitus. Long-term studies in diabetes suggest that angiotensin converting enzyme inhibitors postpone, and may even prevent, progression to overt clinical nephropathy in normotensive diabetic patients with persistent microalbuminuria. So far, there have been no long-term comparative trials on the beneficial effects of different antihypertensive drugs in hypertensive patients with microalbuminuria.

Trials investigating the anti-atherosclerotic effects of antihypertensive drugs.

METHODS OF CURRENT TRIALS: Several ongoing trials are investigating the anti-atherosclerotic effects of antihypertensive drugs in hypertensive patients. Changes in carotid intimal-medial thicknesses and atherosclerotic plaques are being explored by a sensitive quantitative B-mode ultrasound technique. MULTICENTER ISRADIPINE/DIURETIC ATHEROSCLEROSIS STUDY (MIDAS): The results from this pioneering study indicated a slower progression, at least in the first 6 months, of carotid plaques in isradipine-treated patients than in diuretic-treated patients. MIDAS has been particularly valuable in giving information on the rate of growth of intimal-medial thickness in hypertensive patients and on the best end-point to use in carotid ultrasound trials. EUROPEAN LACIDIPINE STUDY ON ATHEROSCLEROSIS (ELSA) AND VERAPAMIL IN HYPERTENSION AND ATHEROSCLEROSIS STUDY (VHAS): Baseline data from these two ongoing studies have provided evidence of the very high prevalence of carotid lesions among hypertensive patients: the prevalence of plaques (defined as a carotid intimal-medial thickness of > or = 1.3 mm) was 83% in ELSA, while in VHAS, in which plaques were defined as an intimal-medial thickness of > 1.5 mm), the plaque prevalence was 37%. These observations emphasize the importance of evaluating the atherosclerotic action of antihypertensive agents. PLAQUE HYPERTENSION LIPID-LOWERING ITALIAN STUDY (PHYLLIS): This trial is using a factorial design to explore the anti-atherosclerotic action of an angiotensin converting enzyme (ACE) inhibitor (fosinopril) versus a diuretic, and also intends to evaluate the possible benefits of associating antihypertensive therapy with a statin to induce lipid-lowering to prevent the progression of carotid atherosclerosis.

Effects of long-term cilazapril treatment on glucose and lipid metabolism in hypertensive patients with non—insulin-dependent diabetes mellitus

The effects of long-term cilazapril treatment on glucose and lipid metabolism were assessed in 25 hypertensive patients with non—insulin-dependent diabetes mellitus (NIDDM). Patients were treated with 0.5 to 1 mg of cilazapril once daily or a combination of cilazapril and other anti-hypertensive drugs once daily for 48 weeks. Both systolic and diastolic blood pressures were significantly reduced ( P < 0.001) throughout the study with no significant changes in heart rate and no adverse effects such as cough. There were no significant changes in body mass index or serum levels of glycated hemoglobin A 1c, fructosamine, total cholesterol, triglycerides, lipoproteins (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol), or apolipoproteins (apo A-I, apo C-II, apo C-III, apo B, and apo E). Cilazapril caused a significant increase ( P < 0.05) in levels of apo A-II and a significant decrease ( P < 0.05) in the apo B:apo A-I ratio, an index of arteriosclerosis. These results suggest that cilazapril has favorable effects on glucose and lipid metabolism and that it may be useful as the first or second choice of antihypertensive drugs in hypertensive patients with NIDDM.