摘要:

Genetic variation in the Y chromosome has significant effects on male blood pressure in experimental animals, but the effects in humans are unknown. We examined the relationship between blood pressure and a polymorphicHindIII restriction site in the nonrecombining region of the Y chromosome in 409 randomly selected men from the general population. Carefully standardized measures of systolic and diastolic blood pressures were made. TheHindIII restriction site was significantly more common (43.2%) in men in the lowest decile of the diastolic blood pressure distribution than men in the highest decile (15.9%,P=0.007). No significant difference in genotype frequency was observed between the lowest and highest deciles for systolic pressure (32.4% versus 27.8%,P=0.66). In the entire group, men with theHindIII restriction site had significantly lower diastolic blood pressures (81.2 mm Hg, SD:8.3, versus 83.2 mm Hg, SD:8.7,P=0.03). No significant differences in systolic blood pressure (130.6 mm Hg, SD:14.7, versus 128.3 mm Hg, SD: 13.6) were observed in relation to genotypes. Our results indicate that genetic variation in the human Y chromosome is associated with high blood pressure and contributes significantly to the quantitative variation of male diastolic blood pressure in the general population.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

In a previous study, by using a candidate gene approach, we detected in both Milan hypertensive rats and humans a polymorphism in the &agr;-adducin gene (ADD1) that was associated with blood pressure and renal sodium handling. In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain × Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1,Add2, andAdd3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure. The influence of 2 different methods of blood pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 onAdd1locus (LOD=3.2). A QTL for SBP measured at the tail (indirect SBP) was found on rat chromosome 10 around D10Rat33 (LOD=5.0). All of these QTLs identified chromosomal regions not detected in other rat studies and harbor genes (Na+/H+exchanger A3; &agr;-adducin; &agr;1B-adrenergic receptor) that may be involved in blood pressure regulation. Therefore, these findings may be relevant to human hypertension, also in consideration of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identification of &agr;-adducin as a candidate gene in both species.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The relations between left ventricular mass (LVM) with age, gender, body size, and blood pressure were investigated in healthy adults and children from 149 nuclear families. LVM was strongly correlated with overall weight, especially in the children. Genetic analysis indicated that the segregation of LVM was compatible with an additive polygenic model, with a heritability estimate of 34% before adjustment for weight and 28% after adjustment for weight. Genetic and/or familial environmental factors played a strong role in the correlation of LVM and weight; they accounted for all of the correlation between the 2 traits in adults and 59% of the correlation in children. Spouses exhibited a strong correlation in their weight, which suggested that common family environment may contribute to the family correlations and to the observed heritability of the trait. LVM was strongly correlated with blood pressure before adjustment for weight, but this correlation could be attributed to nonfamilial environment rather than genetic factors. After adjustment for weight, the intertrait correlations between LVM and blood pressure were nonsignificant. Thus, adjustment for weight accounts for all common determinants of LVM and blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Angiotensin II recruits transforming growth factor &bgr;1(TGF&bgr;1) and is related to left ventricular fibrosis. However, it is unclear whether chronic in vivo reduction in left ventricular TGF&bgr;1expression blunts fibrosis and improves outcome in angiotensin II–dependent hypertension. Four-week-old male hypertensive TGR(mRen2)27 (Ren2) rats received either normal food, low-dose losartan (0.5 mg · kg−1· d−1), or tranilast (a nonspecific TGF&bgr; inhibitor; 400 mg · kg−1· d−1) (n=10 for each group) for 12 weeks and were compared with Sprague-Dawley control rats. The effect of tranilast on survival was evaluated in 34 additional untreated homozygous Ren2 rats. Tranilast or low-dose losartan did not lower blood pressure. However, the increase in left ventricular weight (Ren2 versus SD 3.1±0.16 versus 2.1± 0.06 mg/g body wt;P<0.05) was significantly (P<0.05) blunted by both tranilast (2.7±0.05) and losartan (2.7±0.07). Both drugs prevented the increase in left ventricular TGF&bgr;1mRNA and fibronectin mRNA and blunted the increase in hydroxyproline content and the increase in perivascular fibrosis. The perivascular fibrosis score correlated significantly with the level of expression of TGF&bgr;1(r=0.62;P=0.019). In situ hybridization demonstrated increases in TGF&bgr;1mRNA, predominantly in perivascular and nonmyocyte areas. Both drugs did not prevent the decrease in systolic or diastolic dP/dt, but tranilast significantly improved the survival of untreated Ren2 rats (P=0.029). In conclusion, TGF&bgr;1mRNA expression is increased predominantly in nonmyocyte regions in the hypertrophied left ventricle in this angiotensin II–dependent model of hypertension. This increase is probably due to high angiotensin II levels rather than to hypertension. This is the first study to suggest that chronic inhibition of TGF&bgr;1expression attenuates left ventricular hypertrophy and fibrosis, even without lowering blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Despite normal indices of left ventricular (LV) chamber function, patients with LV hypertrophy (LVH) due to hypertension are thought to have depressed midwall systolic shortening compared with normotensives. The aims of the present study were (1) to confirm this observation and (2) to assess the effects of antihypertensive therapy that cause regression of LVH on LV systolic function assessed at both the midwall and endocardium. Thirty-eight previously untreated hypertensive subjects with LVH underwent echocardiography and were compared with 38 normotensive control subjects. Comparisons between the group with LVH and the control group revealed no significant differences in cardiac output (4.32±0.23 versus 4.55±0.21 L/min), ejection fraction (62.5±2% versus 66.4±1.07%), or endocardial fractional shortening (34.5±1.45% versus 37.0±0.82%), but shortening assessed at the midwall was significantly less in the group with LVH (17.9±1.11% versus 21.6±0.63%,P<0.01). Subsequently, 32 patients with uncontrolled hypertension (24 previously untreated and 8 on existing antihypertensive therapy) underwent treatment with ramipril, with the addition of felodipine and bendrofluazide if required, to reduce blood pressure to <140/90 mm Hg. These 32 patients underwent echocardiography at baseline, after blood pressure control, and after an additional 6 months of tight blood pressure control. Good blood pressure control was achieved after 6 months compared with baseline (143/86±2.8/1.4 versus 174/103±4.1/1.9 mm Hg;P<0.01) with significant regression of LV mass index (124±3.4 versus 145±3.8 g/m2,P<0.01). LV fractional shortening assessed at the midwall improved with regression of LVH (21.9±0.84 and 18.7±1.19%,P<0.05), with posttreatment midwall shortening being similar to that of the normal control subjects evaluated in the first study. Hypertensive patients with LVH have depressed midwall systolic shortening despite normal indices of LV chamber function. Regression of LVH after good blood pressure control improved midwall shortening to normal levels.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The study aim was to quantify the individual and combined contributions of both the arterial system and the heart to systolic blood pressure in hypertension. We assessed the parameters of a heart–arterial model for normotensive control subjects and hypertensive patients with left ventricular adaptation patterns classified as normal, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy. The present simulations show that vascular stiffening alone increases the pulse pressure without increasing systolic blood pressure. It is only in combination with an increased peripheral resistance that arterial stiffening leads to systolic hypertension in concentric remodeling and concentric hypertrophy. The contribution of cardiac pump function to the increase in blood pressure depends on cardiac remodeling, hypertrophy, or both. In hypertensive patients with a normal left ventricle, the heart is responsible for 55% of the increase in systolic blood pressure. In concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, the cardiac contribution to the increase in systolic blood pressure is 21%, 65%, and 108%, respectively. We conclude that along with arterial changes, cardiac remodeling and hypertrophy contribute to hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of atenolol on the reduction of cardiovascular morbidity and mortality. A total of 9194 patients with hypertension and ECG left ventricular hypertrophy (LVH) by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria were enrolled in the study, with baseline clinical and ECG data available in 8785 patients (54% women; mean age, 67±7 years). ECG LVH by Cornell voltage-duration product criteria was present in 5791 patients (65.9%) and by Sokolow-Lyon voltage in 2025 patients (23.1%). Compared with patients without ECG LVH by Cornell voltage-duration product criteria, patients with ECG LVH by this method were older; more obese; more likely to be female, white, and to have never smoked; more likely to be diabetic and have angina; and had slightly higher systolic, diastolic, and pulse blood pressures. In contrast, patients with ECG LVH by Sokolow-Lyon criteria were slightly younger; less obese; more likely to be male, black, and current smokers; less likely to have diabetes; more likely to have angina and a history of cerebrovascular disease; and had higher systolic and pulse blood pressure but slightly lower diastolic blood pressure than patients without ECG LVH by this method. By use of multivariate logistic regression analyses, presence of ECG LVH by Cornell voltage-duration product criteria was predominantly associated with higher body mass index, increased age, and female gender, whereas presence of ECG LVH by Sokolow-Lyon voltage criteria was predominantly related to lower body mass index, male gender, and black race. Thus, hypertensive patients who meet Cornell product and Sokolow-Lyon voltage criteria are associated with different, but potentially equally adverse, risk factor profiles.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Echocardiographic studies suggest that women appear to exhibit a greater degree of myocardial hypertrophy in response to increased afterload than men. Therefore, gender differences and the role of estrogen and testosterone in the development of myocardial hypertrophy were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Male and female rats were either surgically neutered or underwent a sham operation at 21 days of age. A subgroup of neutered females of each strain received 17&bgr;-estradiol replacement. At 6 months, the heart weight–to–body weight ratio was assessed and correlated with systemic blood pressure. Compared with males, females had significantly smaller body and heart weights in both normotensive and hypertensive strains. Despite this, females consistently had significantly greater heart weight–to–body weight ratios. In females, neutering significantly lowered the heart weight–to–body weight ratio in WKY rats, which was returned to intact levels with estrogen replacement. Female SHR showed similar, but not statistically significant, responses. In males, neutering appeared to result in a higher heart weight–to–body weight ratio in WKY rats, but the opposite was seen in SHR. In addition, there was a significant correlation between arterial blood pressure and heart weight–to–body weight ratio (systolicr=0.45,P=0.0015: diastolicr=0.52,P=0.0002) in intact males and females of both strains, and for a given diastolic pressure, females always exhibited a greater heart weight–to–body weight ratio than males. Thus, a greater degree of myocardial hypertrophy in females appears to be related to the presence of estrogen in both normotensive and hypertensive rats. Females show a stronger relationship between heart/body weight and blood pressure than males, which occurred independent of the presence of estrogen.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Little is known about the patterns of treatment and adequacy of blood pressure control in older women. The Women’s Health Initiative, a 40-center national study of risk factors and prevention of heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women, provides a unique opportunity to examine these issues in the largest, multiethnic, best-characterized such cohort. Baseline data from the initial 98 705 women, aged 50 to 79 years, enrolled were analyzed to relate prevalence, treatment, and control of hypertension to demographic, clinical, and risk-factor covariates, and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders. Overall, 37.8% of the women had hypertension, which is defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg or being on medication for high blood pressure; 64.3% were treated with drugs, and blood pressure was controlled in only 36.1% of the hypertensive women, with lower rates of control in the oldest group. After adjustment for multiple covariates, current hormone users had higher prevalence than did nonusers (odds ratio 1.25). Hypertensive women had more comorbid conditions than did nonhypertensive women, and women with comorbidities were more likely to be treated pharmacologically. Diuretics were used by 44.3% of hypertensives either as monotherapy or in combination with other drug classes. As monotherapy, calcium channel blockers were used in 16%, angiotensin-converting enzyme inhibitors in 14%, &bgr;-blockers in 9%, and diuretics in 14% of the hypertensive women. Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy. In conclusion, hypertension in older women is not being treated aggressively enough because a large proportion, especially those most at risk for stroke and heart disease by virtue of age, does not have sufficient blood pressure control.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The association between low birth weight and raised blood pressure has been extensively replicated. Little is known about the way childhood growth modifies the effects of low birth weight. We report on the fetal and childhood growth of 1958 men and women who received treatment for hypertension and belong to a cohort of 7086 people born in Helsinki, Finland, during 1924–1933. As expected, the men and women who developed hypertension had low birth weight (P=0.002). They were also shorter in body length at birth (P=0.02). After birth they experienced accelerated growth, so that by 7 years their heights and weights were approximately average. In a simultaneous regression, both birth length and tall height had statistically significant although opposing effects on hypertension (P=0.003 for birth length and 0.009 for height at 7 years). Accelerated postnatal growth was associated with better childhood living conditions. Children who later developed both hypertension and type 2 diabetes, rather than hypertension alone, had small placental size as well as small body size at birth, and their accelerated postnatal growth continued beyond 7 years. We suggest that hypertension may originate through retarded growth in utero followed by accelerated postnatal growth as a result of good living conditions. Retarded fetal growth leads to permanently reduced cell numbers in the kidney and other tissues, and subsequent accelerated growth may lead to excessive metabolic demand on this limited cell mass.

ISSN:0194-911X    

出版商:OVID    

年代:2000

数据来源: OVID