摘要:

Pharmacogenetic investigation seeks to identify genetic factors that contribute to interpatient and interdrug variation in responses to antihypertensive drug therapy. Classical studies have characterized single gene polymorphisms of drug metabolizing enzymes that are responsible for large interindividual differences in pharmacokinetic responses to several antihypertensive drugs. Progress is being made using candidate gene and genome scanning approaches to identify and characterize many additional genes influencing pharmacodynamic mechanisms that contribute to interindividual differences in responses to antihypertensive drug therapy. Knowledge of polymorphic variation in these genes will help to predict individual patients’ blood pressure responses to antihypertensive drug therapy and may also provide new insights into molecular mechanisms responsible for elevation of blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo establish the factors affecting the difference between screening and home blood pressure measurements.DesignA cross-sectional study.SettingGeneral population in a rural Japanese community, Ohasama, Japan.ParticipantsThere were 1789 community-based subjects aged⩾40 years, for whom blood pressure was measured at screening site (screening blood pressure) and at home (home blood pressure).ResultsMultiple stepwise regression analysis of all subjects demonstrated that screening pulse pressure was positively associated with the difference between screening and home blood pressure measurements for systolic blood pressure. Age, the use of antihypertensive medication, and smoking status were negatively associated with the difference between measurements of both systolic and diastolic blood pressure.ConclusionWe have demonstrated that age, smoking, antihypertensive medication, and screening pulse pressure are independent predictors of the magnitude of the difference between screening and home blood pressure measurements, suggesting that the necessity to consider these factors, for the detection of the subjects who may be inappropriately treated or misjudged following screening blood pressure measurements.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesThe goal of this study was to compare the cardiovascular responses to behavioural stressors of three groups of adolescents who differed in blood pressure status across assessments.DesignCasual blood pressure of adolescents who were identified as having elevated blood pressure during a school screen was re-evaluated in the laboratory. The adolescents were classified into two groups: (i) those with consistently elevated blood pressure across school and laboratory assessments and (i) those with labile blood pressure whose blood pressure in the laboratory was below 130/80 mmHg. A comparison group of adolescents with consistently normal blood pressure was also included.MethodsCardiovascular parameters were assessed during rest and during two behavioural stressors, the evaluated speaking task and the mirror tracing task.ResultsAdolescents with elevated blood pressure were more vascularly responsive across stressors than adolescents with labile blood pressure, who, in turn, were more reactive than adolescents with normal blood pressure.ConclusionsThese results suggest that vascular reactivity to behavioural stressors may be useful in predicting risk of hypertension because of its sensitivity in distinguishing adolescents with consistently elevated blood pressure from those with labile blood pressure and those with normal blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the link between maternal diet during pregnancy and blood pressure of the offspring.DesignFollow-up study.SettingA university hospital in Amsterdam, The Netherlands.ParticipantsPeople born at term as singletons between November 1943 and February 1947.Main outcome measureBlood pressure at adult age.ResultsAdult blood pressure was not associated with protein, carbohydrate or fat intake during any period of gestation. We found, however, after adjustment for sex that the systolic blood pressure decreased by 0.6 mmHg (0.1–1.1) for every 1% increase in protein/carbohydrate ratio in the third trimester. This association was present both in people who had been exposed to the famine during gestation as well as in those who had not been exposed. The association between protein/carbohydrate ratio in the third trimester and adult blood pressure was furthermore independent of maternal weight gain and final weight, and birth weight [increase for every 1% increase in protein/carbohydrate ratio 0.6 mmHg (0.0–1.2)]. Adjustment for adult characteristics such as body mass index, smoking and socio-economic status did not affect the observed association appreciably [adjusted increase 0.5 mmHg (0.0–1.0)].ConclusionAdult blood pressure seems to be affected by small variations in the balance of macro-nutrients in the maternal diet during gestation rather than by relatively large variations in the absolute amounts.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundElevated blood pressure is an established risk factor of cardiovascular diseases, but there is a constant debate whether the association is continuous or with a threshold.MethodsDuring the 1960s (1964 onwards), 3267 initially healthy male business executives (born 1919–1934) participated in voluntary health check-ups with measurements of cardiovascular disease risk factors. At baseline none of the men were on antihypertensive medication. Mortality follow-up was performed using national registers up to 31 December, 1995. Follow-up total and cardiovascular mortality was related to systolic (by 10 mmHg) and diastolic (by 5 mmHg, Korotkoff's 4th phase) blood pressure at baseline. Analyses were adjusted for age, body mass index, smoking and serum cholesterol.ResultsDuring an up to 32-year follow-up, there were 701 deaths, 234 (33.4%) of them due to coronary heart disease, 49 (7.0%) to stroke, 42 (6.0%) to other cardiovascular diseases and 204 (29.1%) to cancer. Total mortality curves of the whole cohort (all age groups) were flat until 131–140 mmHg (systolic) and 81–85 (diastolic) and increased thereafter. Among men who smoked and had baseline serum cholesterol>6.5 mmol/l (n =986), the risk of death increased progressively with systolic blood pressure, whereas among non-smoking normocholesterolaemic men (n =504) the association was J-shaped, i.e. higher mortality at⩽110 mmHg than between 111–150 mmHg and a more consistent rise from 151–160 mmHg. The curves were essentially similar for cardiovascular mortality. The results were supported by analyses where major cardiovascular risk factors were controlled.ConclusionDuring a truly long-term follow-up, the relationship between systolic blood pressure and mortality was initially flat up to 131–140 mmHg although a linear relationship is suggested in men with other cardiovascular risk factors.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk.DesignCross-site comparison using standardized measurement and techniques.SettingRural and urban Cameroon; Jamaica; Manchester, Britain.SubjectsRepresentative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester.Main outcome measuresCross-site age-adjusted prevalence; population attributable risk.ResultsAmong 1587 men and 2087 women, age-adjusted rates of blood pressure⩾160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British- Caribbean-origin women. Sub-optimal blood pressure control (>140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available.ConclusionWith mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundThe studies on the association of deletion/insertion (D/I) polymorphism of angiotensin converting enzyme (ACE) gene with blood pressure and hypertension reported contradictory results. Because there was no population-based study in Japan, we examine the hypothesized association in a cross-sectional sample of a Japanese cohort.Methods and resultsThe blood pressure of 464 men and 876 women aged 40–80 years was measured, and their DNA was analyzed forACED/Igenotypes. The prevalence of theDallele was 38.7 and 39.2% in men and women, respectively (overall 39%). There was a tendency for higher covariate (age, body mass index, albuminuria, hematocrit, alcohol consumption, smoking, diabetes mellitus, ischemic heart disease and antihypertensive medication) adjusted mean levels of diastolic blood pressure for theDDgenotype in men but not in women. However, this tendency disappeared after dichotomization of blood pressure into diagnostic categories (normotension and hypertension). Results did not differ when the subjects were divided into two age groups (⩽59 and⩾60 years). Covariate-adjusted odds ratios for hypertension for presence of theDallele were close to the null value of one.ACEgenetic variation accounted for only 0.1 and 0.7% of the inter-individual variation in systolic and diastolic blood pressure in men. These estimates were 0.2 and 0.1%, respectively, in women.ConclusionAlthough there is a tendency of higher diastolic blood pressure in men withDDgenotypes, there is no convincing evidence thatACEgenotypes are associated with hypertension in this Japanese population.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo identify chromosome regions containing hypertension susceptibility genes in Chinese.Subjects and methodsA three-stage study was carried out in Chinese siblings ascertained through outpatient clinics. In the first stage, 283 affected sib-pairs from 79 nuclear families were subjected to a genome-wide scan with 240 microsatellite marker loci. The second stage focused on chromosome 2 with additional markers resulting in an average distance of 5 cM and used an independent sample of 637 affected sib-pairs from 161 families. In the third stage, a fine-scale mapping study on the suggestive region was performed in an independent set of 777 affected sib-pairs from 106 families. Fourteen markers were used with an average distance less than 2 cM. Non-parametric linkage analyses (NPL), parametric linkage analyses and transmission-disequilibrium tests were used to assess evidence for linkage and association.ResultsThree markers (D2S168 at 27.06 cM, D2S151 at 152.04 cM and D2S142 at 161.26 cM) on chromosome 2 with suggestive linkage to hypertension susceptibility genes were identified in the genome-wide scan. In stage II, the suggestive region around D2S151 and D2S142 was replicated, while the linkage around D2S168 was not. In the stage III fine-scale mapping study, multipoint linkage analyses showed LOD scores greater than 2.0 throughout a region between 157.16 cM and 162.46 cM (allP<0.001) with a maximum peak of 2.24 (P= 0.00067) at 160.52 cM. We also observed a NPLZ-score peak of 3.27 at 157.55 cM (P= 0.00086).ConclusionsThe results of a suggestive region on chromosome 2q14-q23 (D2S112–D2S2370) were consistent between each of the three studies. Interestingly, this region overlaps a syntenic region that contains blood pressure quantitative trait loci identified in rat models of hypertension. These data suggest that the region near D2S142 and D2S151 deserves to be further screened for hypertension susceptibility genes.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesIn hypertension, the vascular wall undergoes morphological changes that alter mechanical responses to vasoactive substances. Ceramide is a recently identified second messenger synthesized in response to cytokines such as tumour necrosis factor α (TNF-α). It has been previously demonstrated that vascular smooth muscle cells (VSMC) from genetically hypertensive rats proliferate at a higher rate than those of normotensive origin. We tested the hypothesis that the ceramide pathway is impaired in VSMC from spontaneously hypertensive rats (SHR).DesignVSMC were isolated from aortae of SHR and from Wistar–Kyoto (WKY) rats. Ceramide levels were measured under baseline and agonist-stimulated conditions and cell proliferation was monitored.MethodsCell proliferation was determined by cell counting. Ceramide levels were determined via radioactive labelling, high-performance thin-layer chromatography and phosphorimaging. Relative mRNA levels of neutral sphingomyelinase were determined using semi-quantitative polymerase chain reaction (PCR).ResultsBasal ceramide levels in untreated cells were lower in cells from SHR compared to WKY rats. During chronic treatment with TNF-α, ceramide levels increased in WKY rat cells but remained unchanged in cells from SHR. TNF-α treatment had an inhibitory effect on WKY rat VSMC proliferation, but stimulated proliferation in cells from SHR. Short-term incubation with TNF-α resulted in a greater increase in ceramide in cells from WKY rats than those from SHR. Semiquantitative PCR analysis indicated that neutral sphingomyelinase mRNA may be reduced in SHR VSMC.ConclusionsWe conclude that ceramide synthesis is impaired in vascular smooth muscle from SHR and may contribute to increased VSMC proliferation in hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundExercise training induces cardiovascular changes that are both generalized and restricted to the microcirculation of the tissues more actively involved in the exercise itself. Whether the local effect of exercise extends to larger arteries is unknown, however.MethodsIn the right and left upper limb of 17 right-handed subjects performing an asymmetric training of the upper limbs (hammer throwers and baseball players) and 16 age-matched sedentary controls, we continuously measured radial artery diameter, distensibility and wall thickness by an echotracking and a beat-to-beat finger blood pressure device. Arterial distensibility was calculated by the arctangent model of Langewouters and expressed as continuous values from diastolic to systolic blood pressure. Measurements were made: (1) in baseline conditions; (2) after release from prolonged proximal ischaemia; and (3) after an increase in radial artery blood flow caused by a short (4 min) distal ischaemia to determine the endothelial involvement in the training-induced change in arterial distensibility.ResultsIn athletes the radial artery distensibility was markedly greater in the right than in the left arm, the latter showing values slightly greater than those seen in the two arms of sedentary subjects. In both arms and groups radial artery distensibility increased markedly after prolonged ischaemia, the between arm and group differences being preserved, however. The radial artery response to distal short ischaemia was, on the other hand, similar in the two arms of the athletes, although greater in these subjects than in the sedentary ones. Radial artery wall thickness was greater in the trained than in the untrained arm of athletes, both values being greater than in sedentary subjects.ConclusionsAsymmetrical training of the upper limbs is accompanied by a greater distensibility of the middle-sized arteries of the more trained side. This is not associated with asymmetrical changes in endothelial structure or function. It is associated with a greater wall thickness in the trained side, suggesting that, at least in part, a training-induced asymmetrical change in wall structure (possibly with a predominance of more distensible tissues such as elastine and smooth muscle) is responsible.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID