摘要:

Abstract—Left ventricular (LV) mass and geometry predict risk for cardiovascular events in hypertension. Regression of LV hypertrophy (LVH) may imply an important prognostic significance. The relation between changes in LV geometry during antihypertensive treatment and subsequent prognosis has not yet been determined. A total of 436 prospectively identified uncomplicated hypertensive subjects with a baseline and follow-up echocardiogram (last examination 72±38 months apart) were followed for an additional 42±16 months. Their family doctor gave antihypertensive treatment. After the last follow-up echocardiogram, a first cardiovascular event occurred in 71 patients. Persistence of LVH from baseline to follow-up was confirmed as an independent predictor of cardiovascular events. Cardiovascular morbidity and mortality were significantly greater in patients with concentric (relative wall thickness ≥0.44) than in those with eccentric geometry (relative wall thickness <0.44) in patients presenting with LVH (P=0.002) and in those without LVH (P=0.002) at the follow-up echocardiogram. The incidence of cardiovascular events progressively increased from the first to the third tertile of LV mass index at follow-up (partition values 91 and 117 g/m2), but for a similar value of LV mass index it was significantly greater in those with concentric geometry (OR: 4.07; 95% CI: 1.49 to 11.14;P=0.004 in the second tertile; OR: 3.45; 95% CI: 1.62 to 7.32;P=0.001 in the third tertile;P<0.0001 in concentric versus eccentric geometry). Persistence or development of concentric geometry during follow-up may have additional prognostic significance in hypertensive patients with and without LVH.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Excessive myocardial fibrosis deteriorates diastolic function in hypertensive hearts. Involvement of macrophages is suggested in fibrotic process in various diseased situations. We sought to examine the role of macrophages in myocardial remodeling and cardiac dysfunction in pressure-overloaded hearts. In Wistar rats with suprarenal aortic constriction, pressure overload induced perivascular macrophage accumulation and fibroblast proliferation with a peak at day 3, decreasing to lower levels by day 28. Myocyte chemoattractant protein (MCP)-1 mRNA was upregulated after day 1, peaking at day 3 and returning to insignificant levels by day 28, whereas transforming growth factor (TGF)-&bgr; induction was observed after day 3, with a peak at day 7, and remained relatively elevated at day 28. After day 7, concentric left ventricular (LV) hypertrophy developed, associated with reactive fibrosis and myocyte hypertrophy. At day 28, echocardiography showed normal LV fractional shortening but decreased ratio of early to late filling wave of transmitral Doppler velocity, and hemodynamic studies revealed elevated LV end-diastolic pressure, suggesting normal systolic but impaired diastolic function. Chronic treatment with an anti-MCP-1 monoclonal neutralizing antibody inhibited not only macrophage accumulation but also fibroblast proliferation and TGF-&bgr; induction. Furthermore, the neutralizing antibody attenuated myocardial fibrosis, but not myocyte hypertrophy, and ameliorated diastolic dysfunction without affecting blood pressure and systolic function. In conclusion, roles of MCP-1-mediated macrophage accumulation are suggested in myocardial fibrosis in pressure-overloaded hearts through TGF-&bgr;-mediated process. Inhibition of inflammation may be a new strategy to prevent myocardial fibrosis and resultant diastolic dysfunction in hypertensive hearts.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-&agr;. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%±4.8% versus 62.5%±3.3%,P<0.01). The reduction of interstitial fibrosis is accompanied by an increase in myocardial hHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6±7.0, 117.4±3.5, and 110.7±2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-&bgr; and active NF-&kgr;B proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-&bgr; and NF-&kgr;B pathway.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Caffeine acutely raises blood pressure (BP). The clinical significance of this effect depends on whether BP responses persist in persons who consume caffeine on a daily basis. Accordingly, the ability of caffeine to raise BP after 5 days of regular daily intake was tested in a randomized controlled trial. Individual differences in tolerance formation were then examined. Men (n=49) and women (n=48) completed a double-blind, crossover trial conducted over 4 weeks. During each week, subjects abstained for 5 days from dietary caffeine and instead used capsules totaling 0 mg, 300 mg, and 600 mg of caffeine per day in 3 divided doses. On day 6, in the laboratory, they used capsules with either 0 mg or 250 mg of caffeine at 9:00 am and 1:00 pm. Systolic/diastolic BP increases as a result of 250 mg of caffeine remained significant (P<0.006/0.001) at all levels of previous daily consumption. Individual difference comparisons found that although half the subjects had complete loss of systolic and diastolic BP responses to the challenge doses, the other half showed no loss in BP response, even after using 600 mg of caffeine per day for the previous 5 days (F>7.90,P<0.001). The sexes did not differ in degree of tolerance formation. Daily caffeine consumption failed to eliminate the BP response to repeated challenge doses of caffeine in half of the healthy adults who were tested. Caffeine may therefore cause persistent BP effects in persons who are regular consumers, even when daily intake is at moderately high levels.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—A polymorphism in intron 10 of the serine-threonine kinase with no lysine (K) 4 geneWNK4(G→A, base 1156666 on chromosome 17) has recently been associated with essential hypertension in a white American population. We have attempted to replicate this finding in a well characterized cohort of 184 unrelated hypertensive Australians of British extraction in which biological power was enhanced by them each having 2 hypertensive parents. Controls were 219 normotensive ethnically matched subjects whose parents were both normotensive. Genotyping was performed using the homogeneous MassEXTEND Assay. This showed a frequency of 0.10 for the minor allele in each group (P=0.88). Moreover, blood pressure, body mass index, sex, and plasma lipid levels were similar across genotypes. In conclusion, our study provides no support for an association of the intron 10 variant ofWNK4with essential hypertension in the Anglo-Australian population studied.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Echocardiographic left ventricular hypertrophy (Echo-LVH) and ST segment depression (STD) on the ECG have each been demonstrated to predict cardiovascular (CV) and all-cause (AC) mortality. However, the prognostic value of combining Echo-LVH and ECG-STD has not been examined. ECGs and echocardiograms were examined in 2193 American Indian participants in the second Strong Heart Study examination. STD was measured by computer and was considered abnormal if ≥50 &mgr;V. Echo-LVH was defined by indexed LV mass >116 g/m2in men and >104 g/m2in women. After a mean follow-up of 3.1±0.7 years, there were 57 CV and 169 AC deaths. In univariate Cox analyses, Echo-LVH (&khgr;2=54.2 and &khgr;2=68.5) and ECG-STD (&khgr;2=35.9 and &khgr;2=46.3, allP<0.001) predicted CV and AC mortality, respectively. The combination of Echo-LVH and ECG-STD improved risk stratification compared with either alone for both CV death (&khgr;2=74.4,P<0.001) and AC death (&khgr;2=102.0,P<0.001), with presence of both ECG-STD and Echo-LVH associated with the greatest risks. After adjustment for age, sex, and relevant risk factors, combined Echo-LVH and ECG-STD remained predictive of CV mortality (&khgr;2=19.7,P<0.001) and AC mortality (&khgr;2=24.9,P<0.001), with the presence of both Echo-LVH and ECG-STD associated with a 6.3-fold increased risk of CV death (95% CI: 2.8 to 14.2) and a 4.6-fold increased risk of AC mortality (95% CI: 2.5 to 8.5). ECG-STD and Echo-LVH additively increase the risk of both CV mortality and AC mortality. These findings support the value of combining Echo-LVH and ECG-STD to improve risk stratification. These findings require verification in other populations.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Increased left ventricular mass (LVM) and lower socioeconomic status (SES) are predictors of cardiovascular morbidity and mortality. Blacks and Hispanics are more likely to have higher LVM and lower SES. The relation between SES, race–ethnicity, and LVM has not been fully explored. Data were used from the NOMAS population-based sample of 1916 subjects living in Northern Manhattan. SES was characterized on the basis of educational attainment and divided into 4 categories. Echocardiography-defined LVM was indexed according to height at the allometric power of 2.7 and analyzed as a continuous variable. LVM varied by race in our cohort (blacks 48.9 g/m2.7, Hispanics 48.4 g/m2.7, whites 45.6 g/m2.7;P=0.004). Using ANCOVA, there was a significant inverse and graded association between mean LVM and SES for the total cohort. Mean LVM was 48.4 g/m2.7, 48.6 g/m2.7, 47.1 g/m2.7, and 45.3 g/m2.7for the lowest to the highest educational level category (Ptrend=0.0004). This relationship remained among normotensives (Ptrend=0.0005) and was present for blacks (Ptrend=0.009), but not for whites (Ptrend=0.86) or Hispanics (Ptrend=0.47). The difference in mean LVM between the highest and lowest categories of education was 5.3 g/m2.7for blacks, 0.0 g/m2.7for whites, and 1.0 g/m2.7for Hispanics. Lower SES is an independent predictor of increased LVM among hypertensive and normotensive blacks.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Previous analysis in the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart Lung and Blood Institute (NHLBI) Family Blood Pressure Program, a multicenter study of genetic and environmental factors related to hypertension, indicated regions of linkage for blood pressure traits together with several coincident regions for phenotypically correlated traits, including systolic blood pressure (SBP) response to a postural challenge and body mass index (BMI). Motivated by these findings and by our desire to better understand the physiology of these traits, we conducted bivariate linkage analysis of postural SBP change and BMI. Sibships in HyperGEN were recruited from 5 field centers in Massachusetts, North Carolina, Minnesota, Utah, and Alabama. All available affected siblings, their parents, and selected nonmedicated offspring were recruited. Among 1636 whites and 1747 blacks, we performed a maximum likelihood bivariate genome scan for quantitative trait loci influencing postural SBP change and BMI, similarly adjusted for race, study center, sex, age, and age-by-sex interactions. Genome scans were performed using SOLAR (version 2.0) and race-specific marker allele frequencies derived from founders. The maximum genome-wide logarithm of odds (LOD) score of 3.2 was detected on chromosome 13 at 24 cM. This marker (D13S493) lies within 20 cM of a marker previously linked to BMI in the Family Heart Study and is substantially higher than the univariate linkage for each trait (LOD scores for BMI and postural SBP change were 2.4 and 0.9, respectively). These findings suggest that a gene(s) on chromosome 13q jointly regulates the SBP response to postural change and BMI.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Renin release into plasma has been used to investigate the drug dose-dependence of renin-angiotensin system inhibition because it is proportional to the interruption of the permanent negative feedback loop of angiotensin II on renin secretion. We investigated the 24-hour between-subject differences in renin profiles by analyzing the time-dependence of individual renin responses in 16 mildly sodium-depleted normotensive subjects exposed in a 4-period crossover study to single oral doses of 8- and 16-mg (C8 and C16) candesartan cilexetil and 80- and 160-mg (V80 and V160) valsartan. C8 had a similar effect to V160 in terms of the increase in active renin concentration and decrease in blood pressure. C16 had the strongest effect and V80 the weakest effect on renin release. Within- and between-subject variability was more marked for valsartan pharmacokinetics than for candesartan pharmacokinetics and influenced variability in renin response. To eliminate some of the variability caused by the pharmacokinetics of each drug, we corrected the area under time curve of plasma renin levels by that of plasma drug levels to obtain an individual normalized index of renin release or “renin/pharmacokinetic index”. In these experimental conditions, this index was found to be a reproducible individual characteristic affecting renin response, in addition to the pharmacokinetics and pharmacological properties of angiotensin II type-1 receptor antagonists. The pharmacokinetic–pharmacodynamic model of renin release described here could be of value for the identification and investigation of renin release abnormalities in patients with hypertension and for the comparison of renin-angiotensin system blockers.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID