Haplotype-based case-control study of receptor (calcitonin) activity-modifying protein-1 gene in cerebral infarction.

Calcitonin gene-related peptide (CGRP) receptor is a complex molecule that consists of calcitonin receptor-like receptor and receptor activity-modifying protein-1 (RAMP1). It was recently reported that RAMP1-deficient mice (RAMP1(-/-)) showed inflammatory responses with a transiently significant increase in serum CGRP levels and proinflammatory cytokines when compared with RAMP1(+/+) mice. The aim of this study was to investigate the relationship between the human RAMP1 gene and cerebral infarction (CI) using single-nucleotide polymorphisms (SNPs) in a Japanese population. We selected six SNPs in the human RAMP1 gene (rs3754701, rs3769048, rs7557078, rs1584243, rs10199956 and rs7590387) and performed a case-control study using each SNP and haplotype in 171 CI patients and 234 controls. There were no significant differences in overall distribution of genotype and allele frequencies of the SNPs between the CI and control groups. However, there was a significant difference in overall distribution between the CI and control groups (P<0.001) in the haplotype-based case-control study with the combinations of rs3754701-rs3769048-rs7590387. The T-A-C susceptibility haplotype for CI was significantly more frequent than in the control group (P=0.0024). The results suggest that the T-A-C haplotype is a genetic marker for CI, and that RAMP1 or neighbouring genes are associated with increased susceptibility to CI.

The future profile of health promotion and disease prevention in Japan: based on the study of seniors over age 75.

OBJECTIVES: One of the serious challenges for Japanese healthcare is the aging population. Analysis of health evaluation data, especially of the elderly over 75 years, is considered very important. In view of this prolonged life expectancy in Japan, our government started the new campaign of Healthy Japan 21, of which details are described, and also we will demonstrate the general profile of our perspective cohort study program concerning the new elder citizens in Japan. METHODS AND RESULTS: Our group has started a health evaluation program for those apparently healthy new elder citizens over the age of 75. A ten-year cohort study is in progress, which is designed to accumulate health check-up data annually. The study collects information on physical well being, as well as information on the individual's lifestyle, and social, emotional and spiritual environment. Such health appraisal is of primary importance. Preliminary results will be demonstrated with their special implications in clinical and epidemiological significance. The degree of frailty of the individual was also carefully evaluated, so that we can learn about the QOL of the seniors in Japan. CONCLUSIONS: At the present stage, we can only report a part of our study including the mental and spiritual environments of the individual. This kind of outcome study will give us some insights concerning the natural progress of frailty in the apparently healthy elderly.

Systemic and renal effects of atrial natriuretic peptide in patients with heart failure treated with angiotensin-converting enzyme inhibitor or in acute saline solution loading.

BACKGROUND: Our purpose was to study the effects of atrial natriuretic peptide (ANP) on cardiorenal functions when it is used to manage patients with heart failure who are receiving an angiotensin-converting enzyme inhibitor (ACEi) or in acute saline solution loading. METHODS: Seventeen patients with mild to moderate heart failure were entered into protocol 1 or 2. Protocol 1 was ANP (30 ng/kg/min) infused before and after treatment with ACEi (n = 9). Protocol 2 was acute saline loading with or without coadministration of ANP (n = 8). In both protocols cardiorenal hemodynamics and urinary sodium excretion were assessed before and after each intervention. RESULTS: Protocol 1: Although ANP infusion significantly increased urinary sodium excretion to a similar extent before and after ACEi treatment, the infusion increased the glomerular filtration rate (75 +/- 16 --> 82 +/- 15 mL/min, P <.05) and renal blood flow (390 +/- 123 --> 438 +/- 140 mL/min, P <.05) only before ACEi treatment. Protocol 2: Acute saline solution loading decreased plasma renin activity (P <.05) but did not affect ANP level. Coadministration of ANP with saline solution load enhanced the increase of urinary sodium excretion (75% +/- 34% increase) compared with the acute saline solution load alone (49% +/- 33% increase) (P <.05) but had no affect on renal hemodynamics. CONCLUSIONS: When ANP is used in patients with mild to moderate heart failure who are on combined ACEi treatment or in acute saline solution loading, the vasodilatory effect of ANP is blunted while the natriuretic effect of ANP is preserved. The renin-angiotensin system seems to modulate the vasodilatory effect of ANP.

Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine.

The clinical significance of N-type calcium channel blockade has not been fully examined. We here compared the effects of the N-type calcium channel blockers cilnidipine and amlodipine on the sympathetic nervous system and platelet function in hypertension under resting and stressed conditions. Thirty-two patients with hypertension (58+/-9 years) received cilnidipine or amlodipine for 4 weeks in this crossover study. On day 28 of each treatment, plasma levels of epinephrine (EP), norepinephrine (NEP), and beta-thromboglobulin (BTG), and EC50 of ADP-induced platelet aggregation (ADPE50) were determined at rest and after a cold pressor test. On day 29, the group receiving cilnidipine was switched to amlodipine treatment, and vice versa. At rest, the blood pressure, heart rates, EP, NEP, ADPEC50, and BTG, were similar in both treatments. After the cold pressor test, increases in EP (35+/-17 to 44+/-25 pg/ml; p<0.05) and BTG (40+/-13 to 49+/-22 ng/ml; p<0.01) and a decrease in ADPEC50 (32+/-26 to 27+/-24 micromol; p<0.05) were observed in the amlodipine treatment, but not in the cilnidipine treatment. In addition, the increase in NEP was significantly greater (p<0.05) in the amlodipine (276+/-78 to 318+/-87 pg/ml; p<0.01) than in the cilnidipine treatment (273+/-88 to 291+/-100 pg/ml; p<0.05). Cilnidipine more highly attenuates the activation of platelet function in response to cold pressor stress than does amlodipine. Attenuated activation of the sympathetic nervous system via N-type calcium channel blockade may contribute to this phenomenon.

Diastolic fractional flow reserve to assess the functional severity of moderate coronary artery stenoses: comparison with fractional flow reserve and coronary flow velocity reserve.

BACKGROUND: Coronary blood flow occurs mainly during the diastolic phase of each cardiac cycle and is mainly dependent on diastolic driving pressure, especially in the left anterior descending coronary artery (LAD). We hypothesized that calculation of the ratio of the diastolic driving pressure of a stenotic LAD to its normal value, namely diastolic FFR (d-FFR), might provide precise insight into the mechanism of FFR for assessment of the functional severity of the stenosis. We compared d-FFR with FFR, coronary flow reserve (CFR), and exercise myocardial thallium scintigraphy in an lesion of intermediate severity. METHODS AND RESULTS: The study population consisted of 46 consecutive patients with a moderate stenosis in the LAD in whom simultaneous measurements of aortic pressure, left ventricular pressure, and coronary pressure distal to the stenosis were obtained. Coronary flow velocity was successfully measured with a Doppler guidewire in 37 of the 46 patients. Values for FFR, d-FFR, and CFR in the noninvasive test-positive group were significantly lower than those in the negative group. With cutoff values of 0.75, 0.76, and 2.0 for FFR, d-FFR, and CFR, sensitivities were 83.3%, 95.8%, and 88.2% and specificities were 100%, 100%, and 95.0%, respectively. CONCLUSIONS: The close similarity of the sensitivity and specificity of FFR and d-FFR, around almost identical cutoff values (0.75 versus 0.76), confirms the physiological validity of FFR as a clinical standard. In clinical practice, FFR remains the index of choice for assessment of the functional severity of moderate coronary artery stenoses.

Carotid arterial distensibility is an important determinant of improvement in autonomic balance after successful coronary angioplasty.

OBJECTIVE: To determine whether arterial distensibility influences improvement of autonomic imbalance after left ventricular wall motion (LVWM) abnormality has been improved by percutaneous transluminal angioplasty (PTCA) in patients with ischemic heart disease (IHD). METHODS AND RESULTS: The following variables were assessed before and 3 months after PTCA in 63 patients with IHD who had a successful PTCA: heart rate variability (standard deviation of all normal R-R intervals [SDNN] measured from 24 h Holter electrocardiograms), baroreceptor sensitivity (determined by the phenylephrine injection method), and carotid artery distensibility (determined by ultrasonography). Abnormalities of LVWM were assessed by cineventriculography. In a multivariate analysis, carotid artery distensibility before PTCA and changes in LVWM abnormality before and after PTCA were independently associated with changes in baroreceptor sensitivity and SDNN (P< 0.05). Patients were divided into two groups: one with impaired and one group with unimpaired initial carotid artery distensibility. After PTCA, LVWM was improved significantly in both groups, but baroreceptor sensitivity and SDNN were improved significantly (respectively from 5.0 +/- 3.3 to 5.9 +/- 3.9 ms/mmHg, P< 0.01 and from 111 +/- 47 to 128 +/- 54 ms, P < 0.01) only in patients with well-preserved carotid artery distensibility. CONCLUSIONS: The beneficial effect of PTCA on autonomic balance was greater in patients with well-preserved carotid artery distensibility than in those with impaired carotid artery distensibility. These results suggest that the pathophysiological state of arterial distensibility may modify the autonomic balance even after myocardial ischemia-related LVWM abnormalities are improved.

Close relationship of abnormal glucose tolerance with endothelial dysfunction in hypertension.

Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, and abnormal glucose metabolism. However, no study has examined the relative pathological significance of left ventricular hypertrophy and abnormal glucose metabolism on endothelial dysfunction in hypertension. This study was conducted to evaluate whether abnormal glucose tolerance assessed by 75-g oral glucose tolerance test or left ventricular hypertrophy is more closely associated with endothelial dysfunction in never-treated hypertensive patients without elevated fasting blood glucose. We studied 107 unmedicated hypertensive patients (mean age, 54+/-10 years) whose fasting blood glucose was <7.0 mmol/L. Endothelial function was assessed by change in brachial artery diameter in response to reactive hyperemia, and left ventricular mass index was determined by ultrasonography. Simple linear regression analysis demonstrated that endothelial function significantly correlated with left ventricular mass index and 2-hour blood glucose in 75-g oral glucose tolerance test, but not with fasting blood glucose. Multiple linear regression analysis revealed that endothelial function significantly correlated with 2-hour blood glucose (beta=-2.68, P<0.05) after we controlled for other clinical variables. Patients were divided into 3 groups according to 2-hour blood glucose levels. Endothelial function was more impaired in patients with diabetes (n=12; 4.7+/-1.8%) and in those with impaired glucose tolerance (n=31; 6.3+/-2.9%) than in those with normal glucose tolerance (n=64; 8.4+/-4.5%) (P<0.05), but left ventricular mass index was similar in these 3 groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test, rather than left ventricular hypertrophy, may have direct pathophysiological relevance to endothelial dysfunction in borderline to moderate hypertensive patients.

The effects of monotherapy or combined therapy with an angiotensin converting enzyme inhibitor following initial treatment with calcium channel blockers on residual cardiovascular abnormalities.

The effects of sequential therapy with angiotensin-converting enzyme inhibitor (cilazapril) on left ventricular (LV) mass, LV diastolic function, and carotid artery distensibility were evaluated in 90 hypertensive patients whose blood pressure controlled below 140/90 mmHg with a calcium channel blocker monotherapy. The possibility of predicting the efficacy of cilazapril based on evaluation of biochemical and genetic markers of the renin-angiotensin system was examined. Before cilazapril therapy, LV diastolic function and carotid artery distensibility were significantly impaired in 32 patients with residual LV hypertrophy compared with patients without LV hypertrophy. Cilazapril improved the LV mass in these patients with LV hypertrophy and improved LV diastolic function in a subset of 20 patients with elevated plasma renin activity. Patients with residual LV hypertrophy accompanied by cardiovascular functional abnormalities. Subsequent treatment with cilazapril significantly improved LV morphology and function in those with residual LV hypertrophy or elevated plasma renin activity.

Effects of oral administration of L-arginine on renal function in patients with heart failure.

OBJECTIVES: Although the beneficial effects of L-arginine on systemic haemodynamics have been reported in patients with heart failure, its effect on renal function has not been examined. We evaluated the effects of oral administration of L-arginine on renal haemodynamics, sodium and water handling, and various hormonal factors in patients with chronic heart failure. SUBJECTS AND METHODS: A double-blind crossover trial was performed in 17 patients with chronic congestive heart failure (NYHA II-III, 56 +/- 12 years of age) who were randomly assigned to receive oral L-arginine (15 g/day) and placebo or placebo and arginine sequentially for 5 days each. Twenty-four hour creatinine clearance (Ccr), and 24-h urinary cyclic guanosine 5-monophosphate (GMP) excretion were determined. Saline loading was performed on day 5 of each treatment Renal blood flow, glomerular filtration rate (GFR), and urinary sodium excretion rate (UNa) were assessed before and after saline loading. RESULTS: Twenty-four hour GMP excretion (1.4 +/- 1.1 versus 0.8 +/- 0.5 micromol/day, P < 0.01) and Ccr (150 +/- 43 versus 125 +/- 42 ml/min, P < 0.05) were higher and plasma endothelin level (2.5 +/- 0.6 versus 3.1 +/- 0.8 pg/ml, P < 0.05) was lower with L-arginine treatment compared to placebo treatment In addition, the relative increase of UNa and GFR after saline loading were significantly higher in L-arginine treatment (UNa, 47 +/- 12%; GFR, 44 +/- 31%) than in placebo treatment (UNa, 34 +/- 9%; GFR, 22 +/- 29%) (P < 0.05). CONCLUSIONS: Oral administration of L-arginine has beneficial effects on glomerular filtration rate, natriuresis, and plasma endothelin level in patients with chronic congestive heart failure.

Characteristics of cardiovascular morphology and function in the high-normal subset of hypertension defined by JNC-VI recommendations.

A cross-sectional study was conducted to compare the morphological and functional characteristics of the cardiovascular system among subgroups of hypertension defined by the JNC-VI recommendations. One hundred and sixteen subjects (normotensives and unmedicated hypertensives: 49+/-10 yr) were classified into 4 groups based on the criteria of JNC-VI: normotensive (NOR: n = 38), high-normal blood pressure (HN: n = 16), stage 1 hypertensive (SI: n = 28), and stage 2 to 3 hypertensive (SII-III: n = 34). Ultrasonographic examinations of the heart and carotid artery were performed in all subjects, and the following parameters were obtained: left ventricular mass index (LVMI), relative wall thickness at end-diastole (RWTd), cardiac diastolic function (A/E), common carotid artery diameter (CAD), intimal media thickness of the common carotid artery (IMT), and distensibility of the common carotid artery (Distens). RWTd, A/E, and IMT in SI (RWTd, 0.41+/-0.07; A/E, 1.21+/-0.41; IMT, 0.69+/-0.17 mm) and SII-III patients (0.40+/-0.08, 1.38+/-0.33, 0.80+/-0.21 mm) were larger than those in NOR patients (0.33+/-0.03, 0.86+/-0.21, 0.56+/-0.10 mm) (p < .01). Furthermore, LVMI in SII-III (135.5+/-35.5 g/m2) patients was larger than that in NOR patients (99.4+/-17.5 g/m2) (p < .05). RWTd in HN patients (0.37+/-0.06) was significantly higher than that in NOR patients (p < .05). A/E tended to be larger in HN than in NOR patients (p < 0.1). In the normotensives, no significant difference in any of the parameters was detected between those with optimal (n = 19) and normal (n = 19) blood pressure. Thus, both morphological and functional changes were associated with elevation of blood pressure. Cardiac morphological adaptation and functional impairment were present even in subjects with high-normal blood pressure level, while there were no significant differences between the normal and optimal subsets.

Drugs, heart failure and quality of life: what are we achieving? What should we be trying to achieve?

This article is a review of chronic compensated congestive heart failure (CHF), with special reference to its clinical features and pathophysiology and recent advances in pharmacotherapy, including beta-blockers, loop diuretics, ACE inhibitors and angiotensin II receptor antagonists. Clinical problems related to elderly patients and multifaceted aspects of multidisciplinary approaches of medical care to these particular patients are also discussed with special emphasis on the aspect of improved quality of life associated with reduced mortality. Concepts of CHF have greatly changed over the past decades with regard to its pathophysiology, natural progression, mechanisms, causes of death, arrhythmias and treatment goals. Although the current most frequent aetiologies of CHF include coronary heart disease and dilated cardiomyopathy, hypertension has been revisited in a different way, and has been considered of pivotal importance in most recent trends and possibly in future perspectives. Nowadays, however, with the results of improved survival, alleviation of symptoms, improvement in functional capacity and prevention of associated complications including even left ventricular remodelling through various appropriate pharmacotherapies, patients with CHF are used to being physically and psychosocially more active than ever before. Thus, improvement of patients' quality of life and reduction of mortality have become of prime importance in achieving treatment goals. Another emerging aspect of CHF is aging itself, and special features in the medical care of elderly patients with CHF always have to be taken into consideration in reduction of hospital readmission along with improvement of morbidity and mortality. Despite advances in the treatment of CHF, it remains a common disease with a poor prognosis. Therefore, this review focuses on what we should be trying to achieve in reaching goals to reduce repeated hospital readmission and mortality, and increase social activity and quality of life, especially in elderly patients with CHF. In these clinical settings, educational strategies for patients and their family members should be emphasised. Multidisciplinary interventions by nurses and possibly other contributions from a widely available social support system might be effective in preventing repeated hospital readmissions of elderly patients with CHF. In this regard, special precautions have to be paid in the management of elderly patients to achieve effective treatment goals, and any treatment strategy has to be appropriately determined through a comprehensive assessment of patient clinical profiles. Multidisciplinary approaches to these problems have to be effectively utilised to improve patients' quality of life, while possibly reducing medical expenses.

Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure.

BACKGROUND: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. METHODS: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. RESULTS: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05). CONCLUSIONS: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.

[Cardiac rehabilitation in acute coronary syndrome].

Recently, there have been a great advancement in diagnosis and treatment of ACS, and therefore the modality of cardiac rehabilitation has also been greatly changed. In the era of primary intervention, the hospital stay after ACS has been grossly shortened even within several days. Since morphologies and functions of the diseased coronary arteries and the left ventricle are already correctly and precisely assessed before reaching CCU, the initiation and subsequent progression of cardiac rehabilitation can be performed with great ease. On the contrary to these benefits, however, the time for patients education after ACS is greatly limited. Lifestyle modifications that are thought to be well established key elements in modern preventative cardiology has to be accomplished after discharge from the hospital. These new trends in cardiac rehabilitation must be more efficacious than previous painstaking inhospital rehabilitation procedures and can be accepted widely as economically feasible and safe treatment modalities after ACS.

Effects of an ACE inhibitor and a calcium channel blocker on cardiovascular autonomic nervous system and carotid distensibility in patients with mild to moderate hypertension.

We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension. In 37 patients with hypertension, autonomic function was assessed by heart rate variability and baroreceptor sensitivity using phenylephrine injection. Left ventricular mass index and carotid arterial distensibility were assessed by ultrasound examinations. Before the medication, both baroreceptor sensitivity and heart rate variability correlated with carotid arterial distensibility, but not with left ventricular mass index by multiple regression analysis. Subsequently, patients were randomly allocated into two groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the study, the change in baroreceptor sensitivity correlated with change in carotid arterial distensibility (r = 0.41, P < .05), but not with change in left ventricular mass index. Although derapril and manidipine decreased blood pressure and left ventricular mass index to the same extent, the former improved heart rate variability, baroreceptor sensitivity (5.0 +/- 1.9 --> 5.6 +/- 2.0 msec/mm Hg), and carotid arterial distensibility (2.1 +/- 0.8 --> 2.5 +/- 1.0 %kPa), but the latter did not improve them at all. Thus, impairment of the autonomic balance was related to the impairment of carotid arterial distensibility in hypertension; derapril, but not manidipine, significantly improved these abnormalities.

Relationship between calcium channel antagonists and nocturnal hypotension and autonomic imbalance in patients with a previous myocardial infarction.

The present study was conducted to evaluate the effect of calcium channel antagonists on diurnal changes in blood pressure and on autonomic function in 71 patients who were receiving a calcium channel antagonist because they had previously suffered a myocardial infarction. Ambulatory blood pressures and Holter ECGs were recorded simultaneously for 24 h. Autonomic function was assessed by heart rate variability. Nocturnal systolic pressure was > or = 90 mmHg in 63 patients (group I) and < 90 mmHg in 8 patients (group II). Significant day to night changes in high-frequency power (from 4.3 +/- 1.2 to 4.5 +/- 1.0/m2) as well as in the ratio of low-frequency power to high-frequency power (from 1.3 +/- 0.1 to 1.1 +/- 0.2) were observed in group I. whereas such changes were blunted in group II. When the calcium antagonist was discontinued or the dose was reduced in group II, the autonomic imbalance improved along with elevation of nocturnal systolic blood pressure. Thus, nocturnal blood pressure should be monitored when such drugs are administered for the treatment of ischemic heart disease to a patient with a previous myocardial infarction. If nocturnal hypotension occurs, the dose should be reduced or the drug should be discontinued.

Hormonal and cardiorenal responses to acute saline loading in mild congestive heart failure--the effect of angiotensin converting enzyme inhibition.

We investigated cardiorenal responses to acute saline loading in patients with mild congestive heart failure (CHF) with and without angiotensin-converting enzyme (ACE) inhibition. Saline loading (infusion of 250 ml of normal saline) was performed on 10 patients with mild CHF and 10 control subjects. Although saline loading reduced plasma renin activity and plasma angiotensin II to a similar extent in both groups, it increased cardiac output, renal blood flow, and the ratio of renal blood flow to cardiac output in the mild CHF group but not in the control group. After saline loading, urinary sodium excretion was higher in the control than in the mild CHF group. In the mild CHF group, saline loading was performed again after an ACE inhibitor (delapril) had been administered for 5 days. Although delapril increased cardiac output and renal blood flow under basal conditions, saline loading did not affect these variables. Delapril improved urinary sodium excretion after saline loading. Thus, the renin-angiotensin-aldosterone axis may contribute to cardiorenal hemodynamics and renal sodium handling in patients with mild CHF. This effect may attenuate the natriuretic response to acute saline loading, and administration of an ACE inhibitor improves this attenuation.

Left ventricular geometric patterns and QT dispersion in borderline and mild hypertension: their evolution and regression.

To investigate whether QT dispersion increases in borderline and mild hypertension during a longitudinal observation of > 3 years and whether it is improved with medications, left ventricular geometric patterns and QT dispersion were studied with special regard to their longitudinal changes in 85 male borderline and mild hypertensive subjects with left ventricular mass index < 125 g/m2. These subjects were followed for > 3 years without medication. Thirty-two patients with a left ventricular mass index > 125 g/m2 at the end of follow-up period were further observed using antihypertensive drugs for an additional 3 years. Echocardiograms and electrocardiograms were obtained at the beginning and end of the follow-up period. At the end of the follow-up period, subjects were classified into four groups based on ventricular geometric patterns determined by left ventricular mass index and relative wall thickness in diastole. The QT dispersion was greater in patients with concentric hypertrophy (56+/-18 msec) than in patients with normal geometry (41+/-17 msec) (P < .05) and increased significantly in the former group during the follow-up period. After medication, the left ventricular mass index regressed and the QT dispersion decreased (from 55+/-21 to 50+/-26 msec, P < .01) in these patients. Thus, these findings suggest that changes in the QT dispersion reflect both concentric evolution and regression of left ventricular hypertrophy.

Relationship between endothelial function and fibrinolysis in early hypertension.

Abnormalities in fibrinolysis, endothelial function, and glucose and lipid metabolism have been reported in hypertension. This study was conducted to examine the interrelationships between fibrinolytic factors, glucose and lipid metabolism, and endothelial function in hypertension. The effects of administering an angiotensin converting enzyme inhibitor, benazepril, were also examined. Blood levels of the following substances were measured in patients with borderline and mild hypertension (n=50, 51+/-19 years) and in age-matched controls (n=10): total cholesterol, triglycerides, tissue plasminogen activator activity and antigen, and plasminogen activator inhibitor type 1 activity and antigen. Insulin sensitivity was assessed by oral glucose tolerance test, and endothelial function was assessed by evaluating changes in diameter of the brachial artery during reactive hyperemia as observed by ultrasonography. Activities of tissue plasminogen activator and plasminogen activator inhibitor type 1 were both elevated in the hypertensive patients. Stepwise multiple regression analysis showed that plasminogen activator inhibitor type 1 antigen correlated with insulin sensitivity, total cholesterol levels, and triglycerides levels (P<.01). Endothelial function was negatively correlated with tissue plasminogen activator activity and antigen (P<.01). The chronic administration of benazepril (5-10 mg/d) for 20 weeks improved insulin sensitivity, endothelial function (6.6+/-3.4-->9.0+/-2.5%, P<.01), and tissue plasminogen activator activity and antigen. These results indicate that abnormalities in fibrinolysis are associated with endothelial dysfunction as well as disorders of glucose and lipid metabolism in patients with borderline and mild hypertension. The treatment of such patients with benazepril appeared to improve the impairment in fibrinolysis and endothelial dysfunction.