ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

While the promises of gene therapy may be years away from realization, the therapeutic use of drugs that act by modifying gene transcription is a well-established practice in clinical medicine. Although transcription-modulating drugs are frequently used in many different specialties, the deliberate development and use of these agents in cardiovascular medicine has been comparatively limited. However, research advances in the area of gene transcription and in the molecular genetic regulation of blood pressure, insulin resistance, lipid metabolism, and cell growth are providing new opportunities for controlling the expression of genes that are relevant to the pathogenesis of cardiovascular disease and essential hypertension. These research advances are beginning to converge in the development of transcription-modulating drugs with the potential to attack genetically determined risk factors that often cluster in patients with essential hypertension. Ligand-activated transcription factors that serve as receptors for small lipophilic compounds such as the thiazolidinediones and retinoids represent examples of potential therapeutic targets with direct effects on the expression of genes relevant to the pathogenesis of essential hypertension and its complications. Mounting evidence suggesting that the superior cardiorenal protective properties of converting enzyme inhibitors are related in part to their ability to indirectly modify the expression of genes in the heart and vasculature provides provisional support for the clinical value of this therapeutic approach. Given the success of transcription-modulating drugs in the treatment of type II diabetes and many other clinical disorders, it is anticipated that these agents will be developed as tools for the prevention and treatment of hypertension and cardiovascular disease in the not too distant future. (Hypertension. 1998;32:380-386.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Multiple lines of evidence have suggested that alternative pathways to the angiotensin-converting enzyme (ACE) exists for angiotensin II (Ang II) generation in the heart, large arteries, and the kidney. In vitro studies in intact tissues, homogenates, or membrane isolates from the heart and large arteries have repeatedly demonstrated such pathways, but the issue remains unresolved because the approaches used have not made it possible to extrapolate from the in vitro to the in vivo situation. For our in vivo model, we studied young and healthy human volunteers, for the most part white and male; when these subjects achieved balance on a low salt diet to activate the renin system, the response of renal perfusion to pharmacological interruption of the renin system was studied. With this approach, we studied the renal vasodilator response to 3 ACE inhibitors, 2 renin inhibitors, and 2 Ang II antagonists at the top of their respective dose-response relationships. When these studies were initiated, our premise was that a kinin-dependent mechanism contributed to the renal hemodynamic response to ACE inhibition; therefore, the renal vasodilator response to ACE inhibition would exceed the alternatives. To our surprise, both renin inhibitors and both Ang II antagonists that were studied induced a renal vasodilator response of 140 to 150 mL/min/1.73 m2, [approximate]50% larger than the maximal renal hemodynamic response to ACE inhibition, which was 90 to 100 mL/min/1.73 m2. In light of the data from in vitro systems, our findings indicate that in the intact human kidney, virtually all Ang II generation is renin-dependent but at least 40% of Ang I is converted to Ang II by pathways other than ACE, presumably a chymase, although other enzyme pathways exist. Preliminary data indicate that the non-ACE pathway may be substantially larger in disease states such as diabetes mellitus. One implication of the studies is that at the tissue level, Ang II antagonists have much greater potential for blocking the renin-angiotensin system than does ACE inhibition-with implications for therapeutics. (Hypertension. 1998;32:387-392.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2x2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval [0.87, 2.34], test for trend across all 3 genotypes, P=0.10). In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 [0.34, 0.98] versus usual care) but not for persons with the GG genotype (relative risk=1.2 [0.79, 1.81], test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17). Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension. (Hypertension. 1998;32:393-401.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In the general population, mean systolic and diastolic blood pressure increases up to age 75 years but decreases thereafter. The brain has a role in blood pressure regulation; it is not clear whether the cerebral changes that occur with aging contribute to the decline in blood pressure in the very elderly. We examined a population-based sample of 484 85-year-old persons (344 nondemented and 140 demented, 61 with Alzheimer's disease, 65 with vascular dementia, and 14 with other types of dementia) with a neuropsychiatric examination and blood pressure measurements. Dementia was diagnosed according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised. Brain atrophy was measured by CT of the brain. In the nondemented group, frontal (r=-0.18, P=0.037) and parietal (r=-0.23, P=0.008) cortical atrophy and bifrontal ratio (r=-0.20, P=0.013) were associated with lower systolic blood pressure, and frontal (r=-0.23, P=0.010) and parietal (r=-0.24, P=0.008) cortical atrophy and bifrontal ratio (r=-0.23, P=0.006) with lower diastolic blood pressure. Systolic blood pressure was lower in subjects with Alzheimer's disease and vascular dementia, and diastolic blood pressure was lower in those with vascular dementia compared with the nondemented. Systolic (r=-0.27, P<0.0001) and diastolic (r=-0.10, P=0.020) blood pressure was negatively correlated to dementia severity. In the demented subjects, frontal cortical atrophy was correlated to lower diastolic blood pressure (r=-0.21, P=0.043). Our findings suggest that age-related changes in brain structure may contribute to the decrease in blood pressure in the very elderly and that low blood pressure in dementia disorders is mainly a secondary phenomenon. (Hypertension. 1998;32:404-409.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P<or=to0.01) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% (P<or=to0.004) reduction of all types of end points, including total and cardiovascular mortality. The full relative benefit from nitrendipine was seen as early as 6 months after randomization. To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients. In this analysis, nitrendipine reduced (P<or=to0.05) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33%. Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension. (Hypertension. 1998;32:410-416.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

To evaluate the effects of shift work and race/ethnicity on the diurnal rhythm of blood pressure and urinary catecholamine excretion of healthy female nurses, 37 African American women and 62 women of other races underwent ambulatory blood pressure monitor and urine collection for 24 hours that included a full work shift: day shift (n=61), evening shift (n=11), and night shift (n=27). Awake and sleep times were evaluated from subjects' diaries. Of African Americans, 79% who were working evenings or nights and 32% working day shifts were nondippers (<10% drop in systolic pressure during sleep), whereas only 29% of others working evening+night and 8% working day shifts were nondippers. Regression analyses indicated that evening+night shift workers had a 5.4 mm Hg (P<0.001) smaller drop than day shift workers, and African Americans had a 4.0 mm Hg (P<0.01) smaller drop than others. The odds of an evening+night shift worker being a nondipper were 6.1 times that of a day shift worker (P<0.001), and the odds of an African American were 7.1 times that of others (P<0.001). Total sleep time was significantly greater in the non-African American day shift workers than in the other 3 groups. After controlling for work shift and race/ethnicity, we determined that longer sleep times predicted less dipping (absolute and relative) in blood pressure. Urinary norepinephrine and epinephrine were higher during work than nonwork in both racial groups of day shift workers, but in evening+night shift workers the difference was small and in the opposite direction. These results indicate that being African American and working evening or night shifts are independent predictors of nondipper status. Higher sleep blood pressure may contribute to the known adverse effects of shift work. (Hypertension. 1998;32:417-423.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

or=to0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment. (Hypertension. 1998;32:424-429.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The purpose of this study was to calculate statistically the minimum (base) blood pressure (BP) of nighttime (sleep-time) BP values obtained by ambulatory BP monitoring (ABPM) and to investigate its clinical significance. Twenty-four-hour recording of ECG with ABPM was performed directly (n=89) or indirectly (n=117) in 206 patients with essential hypertension. A telemeter was used for the direct method and a multi-biomedical recorder (TM2425) was used for indirect measurement. First, minimum heart rate (HR0=60/RR0) was determined from sleep-time ECG. The mean product of sleep-time diastolic BP (DBP) and pulse interval (RR) was divided by RR0to obtain DBP0[DBP0=(DBPxRR)s/RR0]. The correlation between systolic BP (SBP) and DBP was used to determine SBP0corresponding to DBP0. Statistical base mean BP (MBP0) was calculated from these values, and its reproducibility and relation to hypertension severity were investigated. MBP0values were similar to true base values of sleep-time MBP obtained by the direct method (mean +/- SD difference, 2.0 +/- 4.2 mm Hg). Direct MBP0criteria predicted hypertension severity (mild, moderate, or severe target organ damage) more accurately (predictive accuracy, 89%) than daytime MBP criteria (53%, P<0.01). Almost the same results were obtained using indirect MBP0criteria. Day-to-day indirect MBP (0) variation (mean absolute difference) was smaller (2.4 +/- 1.8 mm Hg) than day-to-day daytime and nighttime MBP variation (6.3 +/- 5.3 and 5.4 +/- 3.4 mm Hg, respectively; n=61, P<0.01), and the correlation coefficient between day-to-day variations of daytime MBP and physical activity (measured by an acceleration sensor) was 0.38 (P<0.05). In conclusion, statistical base BP was almost equal to true base (minimum) BP of sleep-time BP distribution. It was closely related to the severity of hypertensive organ damage, was highly reproducible, and is considered likely to serve stochastically and physiologically as a representative BP value in an individual subject. (Hypertension. 1998;32:430-436.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID