Antihypertensive Treatment In Patients Research Articles

The role of calcium antagonists in patients with chronic renal failure

The objective of antihypertensive treatment in patients with chronic renal failure, many of whom have elevated blood pressure levels, is to reduce cardiovascular events and to slow down the progression of kidney function impairment. Calcium antagonists have been shown to be effective and safe antihypertensive drugs in patients from different age groups, including children. On the basis of numerous studies, one may conclude that the main benefit of antihypertensive therapy is because of the blood pressure lowering effect per se and that calcium antagonists do not differ from other antihypertensive drugs in the ability to prevent cardiovascular complications of hypertension. In particular, calcium antagonists are not inferior to other groups of antihypertensive agents in the prevention of coronary artery disease. There is, however, now evidence from controlled clinical trials that drugs interfering with the renin-angiotensin system are more beneficial than other antihypertensive agents in patients with chronic renal failure. Thus, several studies have demonstrated that ACE-inhibitors and, in patients with type-2 diabetic nephropathy, AT 1-antagonists are superior to other classes of antihypertensive drugs, including calcium antagonists, in delaying the progression of renal insufficiency. Therefore, in hypertensive patients with chronic renal failure antihypertensive treatment should be initiated with a drug that inhibits the renin-angiotensin system.

Treatment of Tachycardia in Hypertension: Where Do We Stand Now?

Mounting evidence shows that elevated heart rate is associated with a greater risk of developing hypertension and atherosclerosis and that it is a potent predictor of cardiovascular morbidity and mortality. These relationships have been shown not only in general populations but also among hypertensive individuals, with important implications for the treatment of hypertension. Recent evidence suggests that the predictive power of resting heart rate for cardiovascular mortality is even greater than indices derived from analysis of heart rate variability. In spite of this evidence heart rate is still overlooked as a risk factor, but the fact that in most studies the risk related to fast heart rate remained highly significant after controlling for major risk factors for atherosclerosis suggests that it plays a direct role in the induction of the risk. The clustering of several risk factors for coronary artery disease in subjects with fast heart rate suggests that sympathetic overactivity accounts for the increased cardiovascular morbidity in subjects with tachycardia. Moreover, experimental studies both in animals and human beings suggest that the heamodynamic disturbances related to high heart rate have a direct impact on the arterial wall promoting the development and the rupture of atherosclerotic plaques. Data obtained in the experimental animal and pooled data from intervention studies in patients with myocardial infarction or congestive heart failure suggest that drug-induced reduction of heart rate may be beneficial in several clinical conditions. Tachycardia (heart rate ≥ 80 bpm) has been found in over 30% of the hypertensive patients and thus reduction of high heart rate appears as a desirable additional therapeutic goal in a large proportion of the hypertensive population. Several antihypertensive agents have shown good potential for decreasing the fast heart rate in hypertension. In the future, goal of antihypertensive treatment in patients with tachycardia will be to prevent or reverse those functional abnormalities of the autonomic nervous system which accompany the hypertensive condition.

A Prospective Multicenter Study to Evaluate the Feasibility and Safety of Aggressive Antihypertensive Treatment in Patients With Acute Intracerebral Hemorrhage

The authors performed a multicenter prospective observational study to evaluate the feasibility and safety of intravenous antihypertensive protocol for acute hypertension in patients with intracerebral hemorrhage (ICH). Twenty-seven patients with ICH and acute hypertension (mean age 61.37 +/- 14.27; 10 were men) were treated to maintain the systolic blood pressure (BP) below 160 mm Hg and diastolic BP below 90 mm Hg within 24 hours of symptom onset. Neurological deterioration (defined as a decrease in initial Glasgow Coma Scale score > or = 2) was observed in 2 (7.4%) of 27 patients during treatment. Among patients who underwent follow-up computed tomography, hematoma expansion (more than 33% increase in hematoma size at 24 hours) was observed in 2 (9.1%) of 22 patients. Patients treated within 6 hours of symptom onset were more likely to be functionally independent (modified Rankin scale < or = 2) at 1 month compared with patients who were treated between 6 and 24 hours (8 of 18 versus 0 of 9,P = .03). Aggressive pharmacological treatment of acute hypertension in patients with ICH can be initiated early with a low rate of neurological deterioration and hematoma expansion.

Do we need drug therapy to manage mild hypertension in the elderly?

Mild hypertension (grade 1 or stage 1 hypertension) is defined as a systolic blood pressure of 140-159 mm Hg or a diastolic pressure of 90-99 mm Hg. According to current guidelines, patients with mild hypertension can be at low, medium, high or very high risk depending on the presence of other risk factors, target organ damage and associated cardiovascular or renal conditions. Guidelines recommend prompt initiation of antihypertensive treatment in patients at very high risk because of associated clinical conditions and this recommendation is strongly supported by the literature. Also patients at high risk must be treated without much delay, but it should be mentioned that the evidence is stronger for patients who are at high risk because of diabetes mellitus, than for patients at high risk because of left ventricular hypertrophy or the accumulation of >or = 3 other risk factors. Patients at low and medium risk should be followed up and given advice on nonpharmacological measures and treatment should only be initiated in cases of persistently elevated blood pressure. However, this advice is based on indirect evidence and is currently not supported by randomised controlled trials. A survey on treatment of hypertension and implementation of World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in primary care revealed that, respectively, only 20% and 33% of elderly men with mild hypertension at medium and high risk were treated with antihypertensive drugs and that this prevalence amounted to 67% in patients at very high risk; the prevalence was higher in patients with higher levels of blood pressure in each risk category.

Persistence in the antihypertensive treatment in patients treated with irbesartan or other antihypertensive drugs

The aim of this study was to evaluate the incidence of discontinuation and changes in treatment of newly diagnosed hypertensive patients with either the angiotensin II antagonist irbesartan or other antihypertensive drugs. Treated and not treated essential hypertensive patients (EH) were enrolled in the study if BP was ± 140 and/or 90 mmHg in 2 consecutive visits. They were assigned to received irbesartan or some other antihypertensive drug at the usual recommended dose, increasing the dose after 4 weeks if control of BP was not achieved and adding other antihypertensive drugs when necessary. The patients were followed during one year. We calculated the rate of continuation of treatment as well as the decrease of BP and the rate of optimal control (BP<140 and 90 mm Hg) observed in both groups of treatment. Three hundred and sixty- three hypertensives were included in the study. 233 were treated with Irbesartan (I) and 13 with either diuretics (25), betablockers (16), calcium antagonists (26) or ACE inhibitors (63) (Others ). BP at baseline were: I 165± 16/94± 10 mm Hg; Others 158± 14/92± 9 mm Hg (p<0.05 for SBP). See results below. Adverse events were found in 2.4% of EH treated with I and 13,2% of those treated with other antihypertensives (p<0.04). In conclusion, patients treated with irbesartan showed both a higher decrease of BP and persistence in the treatment than patients treated with other antihypertensive drugs. )See Table)

Long-Term Tolerability and Efficacy of the Fixed Combination of Manidipine and Delapril in Patients with Essential Hypertension

Aim: The aim of this study was to assess the long-term tolerability and efficacy of a fixed combination of manidipine 10mg and delapril 30mg (M+D) as an antihypertensive treatment in patients with mild to moderate hypertension.

Antihypertensive treatment in patients with type-2 diabetes mellitus: what guidance from recent controlled randomized trials?

Patients with type-2 diabetes have a high prevalence of hypertension and show an elevated incidence of cardiovascular events and nephropathy. Recent randomized trials of antihypertensive therapy providing information about cardiovascular and renal risk in diabetes, blood pressure goals and best suitable drugs were reviewed. Evidence that association of type-2 diabetes with hypertension markedly increases cardiovascular and renal risk is incontrovertible: even blood pressure values in the high-normal range represent a more relevant risk than in non-diabetics. More versus less intensive blood pressure lowering or active versus placebo treatment can significantly prevent cardiovascular and renal events, with a particularly consistent reduction of proteinuria and microalbuminuria. Although several of the trials showing significant reduction of cardiovascular or renal risk achieved diastolic blood pressure (DBP) between 75 and 82 mmHg, systolic blood pressure (SBP) 140 mmHg was never achieved in trials showing cardiovascular benefits and SBP 130 mmHg was only achieved in two trials in normotensive subjects showing proteinuria reduction. The recommendation given by all major guidelines to lower SBP 130 mmHg appears to be difficult to comply with. Evidence of the superiority or inferiority of different drug classes (angiotensin-converting enzyme inhibitors, calcium antagonists, diuretics and beta-blockers) is rather vague, especially for cardiovascular protection. As to angiotensin-receptor antagonists, losartan has shown significant cardiovascular protection over a beta-blocker, and irbesartan, although not showing cardiovascular benefits over a calcium antagonist, was significantly better in retarding renal dysfunction and failure. In most trials on hypertensive diabetics, the large majority of patients were on two, three and even four-drug therapy. Therefore, it appears reasonable that all effective and well tolerated antihypertensive agents can be used in association to achieve DBP 80 mmHg and, whenever possible, SBP 130 or 135 mmHg, with the regular inclusion of an angiotensin-receptor antagonist for its proven renoprotective action. Hopefully, better guidance will be provided by further trials.

Antihypertensive treatment of patients with diabetes and hypertension

Whereas individual research papers about antihypertensive treatment in diabetics might be somewhat confusing, the weight of the evidence strongly suggests that: 1) In patients with type 1 diabetes, it is advantageous to use angiotensin-converting enzyme (ACE) inhibitors as primary treatment. 2) In type 2 diabetics, aggressive blood pressure (BP) lowering is warranted and, the calcium antagonist controversy notwithstanding, all drugs appear to be similarly useful in reducing cardiovascular mortality. Specifically, in the Systolic Hypertension in Europe study, compared with placebo, a calcium antagonist dramatically reduced cardiovascular (CV) events in elderly diabetics. The Hypertension Optimal Treatment study showed that, using a calcium antagonist-based regimen, the degree of BP lowering determines the degree of CV event reduction. Furthermore, the United Kingdom Prospective Diabetes Study (UKPDS) did not find a difference in CV events reduction in patients treated with β-blockers or with ACE inhibitors. In the UKPDS, the effect of BP lowering on reduction in CV events was more substantial than the degree of CV reduction by blood sugar lowering. 3) Both the CAPtopril Prevention Project (CAPPP) and the Heart Outcomes Prevention Evaluation (HOPE) studies found that treatment with an ACE inhibitor may be useful in reducing the incidence of new-onset type 2 diabetes mellitus. 4) Finally, insulin resistance, a precursor of diabetes mellitus and a strong predictor of future CV disease, is differentially affected by antihypertensive treatment. β-Blockers and diuretics worsen insulin resistance, whereas α-adrenergic blockers and central imidazoline binding agents increase insulin sensitivity. The effect of ACE inhibitors and angiotensin blockers may also positively affect insulin resistance, but the results are not uniformly positive. It stands to reason that the differential effect of various drugs on insulin resistance and primary CV events may be clinically relevant particularly in the course of the long-term prevention of mild hypertension. All current trials investigate the effect of the treatment on secondary prevention of CV events among patients with advanced complicated diabetes and hypertension.

Evolving strategies for renoprotection: diabetic nephropathy

A cumulative incidence of diabetic nephropathy of 25-40% has been documented after duration of diabetes of at least 25 years in both type 1 and type 2 diabetic patients. Diabetic nephropathy has become the leading cause (25-44%) of end-stage renal failure in Europe, the United States and Japan. Until the early 1980s, no renoprotective treatment was available for use in diabetic nephropathy. Death occurred on average 5-7 years after the onset of persistent proteinuria. It should be recalled that development of treatment modalities occurred in reverse order: in the early 1980s, antihypertensive treatment of diabetic nephropathy was introduced, and in the early 1990s, primary and secondary prevention with improved glycaemic control and angiotensin-converting enzyme inhibition. The two main treatment strategies for primary prevention of diabetic nephropathy are improved glycaemic control and blood pressure lowering, particularly using drugs such as angiotensin-converting enzyme inhibitors. Megatrials and meta-analyses have clearly demonstrated the beneficial effect of both the above-mentioned treatment modalities. Secondary prevention, that is, treatment modalities applied to diabetic patients with high risk of development of diabetic nephropathy (e.g. those with microalbuminuria) has been documented, applying angiotensin-converting enzyme inhibitors in both type 1 and type 2 diabetic patients. Furthermore, improved metabolic control reduces the risk of progression. In special cases (such as pancreas transplantation) even reversal of diabetic glomerular lesions has been documented. Antihypertensive treatment of patients with overt nephropathy induces a reduction in albuminuria, a reduction in the rate of decline of glomerular filtration rate, delays development of end-stage renal failure and improves survival. Many potential treatment modalities in preventing and treating diabetic nephropathy are presently being evaluated.

Follow-up study of glomerular dimensions and cortical interstitium in microalbuminuric type 1 diabetic patients with or without antihypertensive treatment.

A decrease in urinary albumin excretion is regularly seen with antihypertensive treatment in patients with diabetic nephropathy. Our study concerns structural data obtained by light microscopy in baseline and follow-up biopsies in antihypertensive treated patients and in a reference group. Microalbuminuric type 1 diabetic patients with diabetes duration of 6-16 years were studied. Two groups, allocated to treatment with either angiotensin-converting enzyme-inhibitor (group 1, n=6) or beta-blocker (group 2, n=6) after the baseline biopsy, were studied in parallel, whereas the reference group (group 3, n=9), without antihypertensive treatment, was part of a previously completed study. The renal plastic-embedded biopsies were serially sectioned (1 microm), the sections being used for determining glomerular volume, vascular pole area, and interstitial space expressed as fraction of tubular cortex. A significant increase in glomerular volume (P=0.04) was seen in group 3 only. Vascular pole area (VPA) and VPA relative to calculated glomerular surface did not show significant changes in any of the groups, only a tendency to increase in VPA in group 3 (P=0.051). The increase in VPA correlated with systolic blood pressure during the study period (r=0.49, P=0.03). Glomerular volume did not correlate with HbA(1C), current diabetic glomerulopathy, or ensuing worsening of glomerulopathy. In group 3 every case showed an increase in interstitium (P=0.0009), group 2 showed a decrease (P=0.03), and group 1 showed no change. Increase in interstitial fractional volume correlated with diastolic blood pressure during the study (r=0.54, P=0.01). In early microalbuminuria, type 1 diabetic patients show glomerular growth, probably compensatory to the developing glomerulopathy. The increase in interstitial volume fraction, demonstrable in early nephropathy, is further augmented over a few years, but is arrested by antihypertensive treatment.

Estudio de los factores relacionados con los cambios en la microalbuminuria durante el tratamiento antihipertensivo

The objective of the present study was to analyze the factors related with changes of microalbuminuria during antihypertensive treatment in patients with essential hypertension. One hundred and six patients (57 men, mean age 40.8 [SD 6.6] years) never treated with antihypertensive treatment were included. At the beginning and after one year, blood pressure biochemical profile and urinary albumin excretion (UAE) were measured. After the initial evaluation, 53 patients received angiotensin converting enzyme inhibitors (ACEi) and 53 beta-blockers (BB). Hydrochlorothiazide was added to achieve the blood pressure target < 140/90 mmHg. The average of UAE was 32.1 (43.1) mg/24 h, and 41 (39%) patients had microalbuminuretics. After 12 months of treatment, a significative fall of systolic BP (-20.6 [8.03] mmHg, p < 0.001), and diastolic BP (-14.18 [10.34] mmHg, p < 0.001) were observed, whereas baseline glucose increases (3.08 [11.07] mg/dl, p = 0.006). The changes of UAE were only related with the baseline UAE values. Neither, age, sex, baseline diastolic BP and changes in diastolic BP were significantly related with the changes in UAE. In spite of similar mean BP reduction (medial BP 17.4 [10.9] vs 14.8 [10.4] mmHg), UAE only was reduced in patients treated with ACEi (LogUAE: 0.203 [0.872] mg/24 h; p < 0.04). In addition, in patients treated with BB a significative increase in baseline glucose (4.4 [12.3] mg/dl; p = 0.013) and uric acid (1.18 [4.18]; p = 0.031) were observed. In patients with essential hypertension, changes in microalbuminuria depends of the initial UAE values and the kind of antihypertensive treatment. ACEi produced higher UAE reduction and lower derangement of the glucose metabolism than BB.

Risk reduction associated with lowering systolic blood pressure: Review of clinical trial data

Hypertension is very common in adults ≥60 years of age. Isolated systolic hypertension (ISH) in particular is a good predictor of events associated with elevated blood pressure such as stroke, coronary heart disease, and congestive heart failure. Two large studies, the Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe study (Syst-Eur), have demonstrated that antihypertensive drug therapy for elderly patients with ISH reduces the risk of stroke and other major cardiovascular events. SHEP demonstrated that antihypertensive drug treatment with a diuretic-based regimen in patients ≥60 years of age with ISH reduced the incidence of total stroke by 36%. SHEP also demonstrated a 32% reduction in the incidence of cardiovascular events for patients receiving active treatment. The 5-year average systolic blood pressure (SBP) was 155 mm Hg in the placebo group (n = 2371) compared with 143 mm Hg for the active treatment group (n = 2365). Results from the recently completed Syst-Eur study also support the benefits of antihypertensive treatment in patients ≥60 years of age with ISH. Active treatment in Syst-Eur consisted of the calcium channel blocker nitrendipine, with the addition of enalapril and hydrochlorothiazide as needed to reduce SBP to <150 mm Hg. In the active treatment group, total stroke decreased by 42%, and all cardiovascular events decreased by 31%. At 2 years, sitting SBP had decreased by 13 mm Hg in the placebo group (n = 2297) compared with 23 mm Hg in the active treatment group (n = 2398). (Am Heart J 1999;138:S225-S230.)

One year of antihypertensive treatment in patients with LVH: the life study.

One year of antihypertensive treatment in patients with LVH: the life study.

Audit of antihypertensive treatment in patients with renal failure.

Recently, intensified antihypertensive treatment has been recommended for patients with proteinuric renal disease, and a target blood pressure of 125/75 mmHg has been proposed. In a retrospective crossectional study, all consecutive patients with renal disease and reduced GFR seen in the renal outpatient clinic Heidelberg during a specified time period were analysed. Physicians administered antihypertensive agents according to their clinical judgment aware of recent recommendations, but without structured guidelines. The aims of the study were: (i) to monitor achieved blood pressure (clinic measurement, self measurement, ambulatory BP measurement); (ii) to monitor the number of antihypertensive medications required; and (iii) to analyse the factors which determine achieved blood pressure and the number of antihypertensive agents required. There were 201 non-transplanted patients, median age 60 years (range 20-86), 131 male, 70 female, median S-creatinine 2.33 mg/dl (1.4-10.9). Fifty-two of the patients had diabetes, 41 GN, 18 ADPKD, 17 vasculitis, seven reflux nephropathy, three analgesic nephropathy and 63 other or unknown renal diseases. When the patients had originally been referred to the renal clinic, median clinic BP had been 160 mmHg systolic (104-260) and 95 mmHg diastolic (65-160). Under nephrological care, achieved clinic systolic (140; 90-190) and diastolic BP values (85; 45-130) were significantly (P<0.0001) lower. Achieved BP was slightly (r=0.23, P<0.05) correlated with age, was not significantly different between genders, and was not correlated to proteinuria, serum creatinine, renal disease or BMI. Average self measured BP values were not different from systolic and diastolic clinic BP values. Ambulatory BP values, however, were significantly (P<0.0001) lower, e.g. daytime systolic BP 133 mmHg (107-171), diastolic 82 mmHg (65-97). A night-time decrease of BP > or = 15% was seen in 18/25 patients only. The median number of antihypertensive classes required was 3 (range 1-7) in non-diabetic and 3.5 (1-7) in diabetic patients, respectively. The number of antihypertensive classes was independent of serum creatinine, BMI or proteinuria, but was significantly (P<0.01) higher in males (4; 1-7) than in females (3; 1-6) and correlated to age (r=27, P<0.01). The study (i) illustrates the difficulty to achieve recommended target BP in patients with renal failure, (ii) shows remarkably little white coat effect on clinic blood pressure, (iii) illustrates the value of ambulatory blood pressure measurement and (iv) documents the importance of multidrug antihypertensive treatment in patients with renal failure.

Differential effects of antihypertensive drugs with differing pharmacological properties on the basal ambulatory blood pressure. Japanese Ambulatory Pressure-ANtihypertensive Effects SEarching study group.

To investigate how antihypertensive drugs with different pharmacological properties affect ambulatory blood pressure (BP) the JAPANESE Study Group developed a database of clinic and ambulatory BPs before and after antihypertensive treatment of patients throughout Japan. Drugs evaluated were nilvadipine (n = 195; b.i.d, 4-8 mg/day), amlodipine (n = 75; q.d., 2.5-10 mg/day), lisinopril (n = 80; q.d., 10-20 mg/day) and bisoprolol (n = 49; q.d., 5-10 mg/day). The relationship between basal ambulatory BP and the hypotensive effect on ambulatory BP during treatment was examined. All antihypertensive drugs significantly decreased both clinic BP and ambulatory BP. The hypotensive effect determined by measurement of clinic BP was significantly greater than that determined by ambulatory BP. The hypotensive effect was positively correlated with basal ambulatory BP. However, there was a quantitative difference in this characteristic among the drugs. The critical daytime systolic ambulatory BP below which a hypotensive effect was not observed was extrapolated to 128, 127 and 124 mm Hg with nilvadipine, amlodipine and bisoprolol, respectively, while that with lisinopril was 97 mm Hg. The slope of the correlation coefficient between basal daytime ambulatory systolic BP and hypotensive effect with lisinopril was significantly smaller than those with the other drugs (P < 0.0001). The slope for the relationship between night-time ambulatory systolic BP and the hypotensive effect with bisoprolol was the steepest (P < 0.0001). Antihypertensive drugs with different pharmacological properties exhibited differing hypotensive effects on the basal ambulatory BP. Such differences in efficacy of the drugs on the basal ambulatory BP may reflect adverse effects of the drugs and the prognosis of hypertension.

Antihypertensive treatment of patients with proteinuric renal diseases: Risks or benefits of calcium channel blockers?

In patients with proteinuric renal diseases the rate of progression of renal insufficiency is determined by the level of blood pressure and proteinuria. It has been demonstrated that strict blood pressure control with angiotensin converting enzyme (ACE)-inhibitors or beta-blockers, aimed at reaching values below 130/80 mm Hg, attenuates the deterioration of renal function. In general, the beneficial effects of these drugs are reflected in a parallel lowering of proteinuria. Calcium channel blockers are effective antihypertensive drugs, however, their safety in patients with proteinuric renal diseases and renal insufficiency may be questioned because of reported untoward effects on urinary protein excretion. The present review discusses the potential benefits and risks of calcium channel blockers (CCBs) in the treatment of patients with renal diseases. To this end we have evaluated the effects of these drugs in animal models of progressive renal injury. In these animal models adverse effects of CCBs have been reported which are attributed to an impairment of autoregulation. In patients with proteinuria, the dihydropyridine CCBs do not lower proteinuria despite a reduction of blood pressure. Studies on the effects on the course of renal function are limited, however, the available data do suggest that this class of CCBs may be less advantageous than other antihypertensive drugs, thus arguing against the use of these agents as first-line drugs in patients with proteinuric renal diseases. Information on the effects of the non-dihydropyridine CCBs is limited to a small number of studies in patients with diabetic renal disease. Although the data suggest that these classes of CCBs might be more beneficial, more studies are needed, particularly in patients with non-diabetic renal diseases, before founded conclusions can be reached.

Changes in Left Ventricular Diastolic Function after Antihypertensive Treatment in Patients with Hypertension

Background：Left ventricular diastolic dysfunction is often observed in hypertensive patients with normal left ventricular systolic function and can cause heart failure symptoms. Doppler echocardiography has become a standard tool for examining left ventricular diastolic function. This study was performed to evaluate the left ventricular diastolic function in hypertensive patients with normal left ventricular systolic function and to determine the changes in left ventricular diastolic function after antihypertensive treatment. Methods：Mitral inflow and pulmonary venous flow velocities were evaluated by transthoracic pulsed-wave Doppler study in patients with hypertension before antihypertensive treatment (n＝50 and after antihypertensive treatment for 4 months(n＝24. The patients were randomly assigned to group I to receive ACE inhibitor or group II to receive other antihypertensive drugs. Results：Before antihypertensive treatment, mitral inflow E/A ratio was 0.94±0.27, deceleration time was 222±47 msec, and pulmonary venous flow S/D ratio was 1.62±0.42. Followup Doppler study was completed in 24 patients after 4 months of antihypertensive treatment. Mitral inflow E/A ratio was significantly increased(0.96±0.24 vs. 1.16±0.25, p<0.001, but deceleration time showed no significant changes. Pulmonary venous flow S/D ratio was significantly decreased(1.75±0.27 vs. 1.50±0.24, p<0.001. There was no significant difference in changes in mitral inflow E/A ratio, deceleration time and pulmonary venous flow S/D ratio between ACE inhibitor group and other antihypertensive group. Conclusion：There was some improvement in left ventricular diastolic function in patients with hypertension after 4 months of antihypertensive treatment. But, there was no significant * 본 논문의 요지는 1997년 대한순환기학회 추계학술대회에서 발표되었음.

Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators.

Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.

Comparative cross-over study of the effects of lisinopril and doxazosin on insulin, glucose and lipoprotein metabolism and the endogenous fibrinolytic system

Objective: The present study was performed to compare the effects of the alpha-1-blocker doxazosin (4 mg/d) with the ACE-inhibitor lisinopril (10 mg/d) in a cross-over study on plasma levels of metabolic and fibrinolytic parameters. Patients, methods: In 10 male patients with upper body obesity, proven stable coronary artery disease and hypertension, measurements included baseline determination of lipoproteins and fibrinolytic parameters and determinations of glucose and insulin during intravenous glucose tolerance tests after two 12-week treatment periods. Results: Basal insulin levels were significantly decreased by both doxazosin and lisinopril (from 15.5±3.5 μU/ml to 11.6±2 μU/ml, P ≤0.05 and from 16.5±2.8 μU/ml to 11.2±2.4 μU/ml, P ≤0.001; respectively). Lisinopril decreased the area under the insulin-concentration time curve by 31.9% ( P ≤0.007) as compared to 23.6% (n.s.) after doxazosin treatment. HDL-cholesterol was increased by lisinopril from 38±3.5 to 43.5±4.4 mg/dl ( P ≤0.05), t-PA antigen was increased by doxazosin from 8.3±0.7 to 11.4±1.6 ng/ml ( P ≤0.05) and PAI-1 was not affected by either therapy. Conclusion: These potentially favorable effects on insulin and lipid metabolism and the endogenous fibrinolytic system might contribute to a higher efficacy of antihypertensive treatment in patients with coronary artery disease and accompanying metabolic cardiovascular risk factors.

A short-term antihypertensive treatment-induced fall in glomerular filtration rate predicts long-term stability of renal function

In long-term intervention studies on renal function outcome an initial decline in the glomerular filtration rate (GFR) may occur after starting therapy. If this initial GFR decline is the result of a treatment-induced hemodynamic change reflecting a fall in intraglomerular pressure, it should be reversible after treatment withdrawal, even after long-term treatment. In fact, it could be beneficial for renal function in the long term. We therefore studied systemic and renal hemodynamics in 40 non-diabetic patients with impaired renal function before treatment, during four years treatment with either atenolol or enalapril, and after withdrawal of that treatment. The acute change in GFR 12 weeks after start of treatment varied widely from -11 to + 11 ml/min (mean +/- SD -1.0 +/- 4.1 ml/min, NS). After four years of treatment, withdrawal for 12 weeks resulted in a rise in GFR of +2.2 +/- 5.4 ml/min, P = 0.011, again with a wide range of +14 to -6 ml/min). The initial fall in GFR was related to the rise after withdrawal (r = 0.32, P < 0.05). Interestingly, the acute treatment induced change in GFR correlated with the long-term slope, such that a patient with a greater initial decline in GFR showed a more stable course during the follow up (r = -0.36, P < 0.05). The patients were arbitrarily divided in group A (N = 20), with the largest initial treatment-induced fall in GFR, and group B (N = 20), with the smallest initial fall in GFR. Group A had a significantly less steep slope than group B (-0.41 +/- 1.52 vs. -2.09 +/- 2.79 ml/min/year, P = 0.023) during the four year follow-up. In group A GFR increased again after withdrawal of treatment (+3.8 +/- 5.6 ml/min, P = 0.011) whereas it did not change in group B (+0.5 +/- 4.0 ml/min, NS). As a consequence, GFR post-treatment was not different compared to pre-treatment in group A (-2.5 +/- 7.2 ml/min, NS), whereas it was 5.9 +/- 12.1 ml/min lower in group B (P = 0.023). Patients treated with enalapril had a similar response as patients treated with atenolol. In conclusion, an initial fall in GFR after starting antihypertensive treatment in patients with a mild to moderate renal function impairment (GFR 30 to 90 ml/min) is reversible even after years of treatment, suggesting that this therapy-induced fall is of hemodynamic and not of structural origin. This initial GFR fall was associated with a subsequent stable renal function. These data lead to the hypothesis that the initial fall in GFR in response to antihypertensive therapy reflects renal protection.