Morning rise of blood pressure assessed by home blood pressure monitoring is associated with left ventricular hypertrophy in hypertensive patients receiving long-term antihypertensive medication.

To assess the influence of morning rise of systolic blood pressure (SBP) as assessed by home blood pressure monitoring on the left ventricular mass index (LVMI) in relation to the blood pressure control status, we evaluated M-mode cardiac echocardiography in 626 hypertensive subjects (412 men and 214 women; mean age, 61.3+/-10.1 years) who were receiving antihypertensive medication. The subjects were requested to measure their blood pressure at home in the morning and evening over a 3-month period. They were distributed into the following four groups by the average (ME Ave) and the difference (ME Dif) of the morning and evening SBP. The well-controlled hypertensives with a morning rise of SBP (ME Ave<135 mmHg and ME Dif>or=10 mmHg; n=45; 7.2%) had a greater LVMI (122.9+/-22.7 vs. 92.7+/-15.6 g/m2, p<0.001) than the well-controlled hypertensives without a morning rise of SBP (ME Ave<135 mmHg and ME Dif<10 mmHg; n=367; 58.6%). The uncontrolled hypertensives with a morning rise of SBP (ME Ave>or=135 mmHg and ME Dif>or=10 mmHg; n=91; 14.5%) also had a greater LVMI (136.8+/-21.9 vs. 100.2+/-17.5 g/m2, p<0.001) than the uncontrolled hypertensives without a morning rise of SBP (ME Ave>or=135 mmHg and ME Dif<10 mmHg; n=123; 19.6%). A stepwise multivariate regression analysis revealed that the ME Dif was the most important factor related to the LVMI (r2=35.1% for all subjects, p<0001; r2=39.7% for men, p<0.001; and r2=18.7% for women, p<0.001). These results suggest that morning rise of blood pressure is an important factor influencing the development of left ventricular hypertrophy in hypertensive patients on antihypertensive medication.     

老年高血压患者降压治疗后舒张压对心脑血管事件的影响

目的探讨老年高血压患者降压治疗后,舒张压水平与心脑血管事件的关系,并了解是否存在关于舒张压的"J"型曲线。方法采用回顾性研究方法将1010例老年高血压患者按降压治疗后舒张压水平分为6组:1组舒张压<65 mm Hg(1 mm Hg=0.1 33 kPa)68例,2组舒张压65～69 mm Hg 154例,3组舒张压70～74 mm Hg 334例,4组舒张压75～79 mm Hg 235例,5组舒张压80～84 mm Hg 148例,6组舒张压85～89 mm Hg 71例;应用Cox比例风险模型分析不同舒张压水平对心脑血管事件的影响。结果 2组心脑血管事件发病率最低,在校正传统危险因素后,与2组比较,4组、5组和6组心脑血管事件发生相对风险分别增加了68%、184%及203%(P<0.05,P<0.01),1组心脑血管事件发生相对风险虽有增加趋势,但差异无统计学意义(P>0.05)。结论老年高血压患者心脑血管事件随降压治疗后舒张压降低有减少趋势,舒张压降至65～69 mm Hg亦能获益。     

Persistence of treatment and blood pressure control in elderly hypertensive patients treated with different classes of antihypertensive drugs

Unsatisfactory blood pressure (BP) control in the treated hypertensive patient is largely related to poor compliance with antihypertensive drug regimens. The aim of the present study was to prospectively evaluate the rate of persistence on treatment and the extent of BP control in 301 elderly, uncomplicated grade I or II hypertensive patients randomly allocated to monotherapy with angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), beta-blockers, angiotensin II receptors (ARBs), or diuretics according to an open-label single-blind study design. After 24 months, the percentage of patients continuing their initial therapy was higher in those treated with ARBs (68.5%) and ACE inhibitors (64.5%) and lower in patients taking diuretics (34.4%; P<.01). The logistic regression model using ARBs as reference term showed that patients treated with ACE inhibitors (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.79-0.99) or CCBs (OR, 0.76; 95% CI, 0.54-0.85) were more likely to continue their initial antihypertensive therapy when compared with those treated with beta-blockers (OR, 0.67; 95% CI, 0.57-0.79) or diuretics (OR, 0.56; 95% CI, 0.38-0.84). The average systolic and diastolic BP decrease was greater in patients treated with ARBs (-11.2+/-4/-5.8+/-2 mm Hg), ACE inhibitors (-10.5+/-4/-5.1+/-2 mm Hg), and CCBs (-8.5+/-3/-4.6+/-2 mm Hg) and lesser in those treated with diuretics (-2.3+/-4/-2.1+/-3 mm Hg, P<.05) and beta-blockers (-4.0+/-2/-2.3+/-2 mm Hg; P<.05). The study confirms the importance of persistence with treatment for the effective management of hypertension in clinical practice.     

不同联合降压方案对高血压患者血压和脉搏波传导速度的影响

目的探讨不同药物的联合降压治疗方案对高血压患者血压和脉搏波传导速度(PWV)的影响。方法选择2008年1～9月在北京医院心内科门诊就诊的高血压患者66例,其中男性36例,女性30例,年龄50～75岁,平均(60.7±7.5)岁。将研究对象随机分为两组:一组患者采用氨氯地平+复方阿米洛利(A组)治疗,另一组患者采用氨氯地平+替米沙坦(B组)治疗。观察不同的联合降压方案对血压、心率、肱踝动脉PWV(baPWV)、血脂、血糖、肌酐和尿酸的影响。结果两种治疗方案均有良好的降压作用,A组平均收缩压和舒张压由(154.4±12.7)mm Hg和(89.1±7.4)mm Hg分别降至(127.7±11.2)mm Hg和(74.8±8.8)mm Hg(均为P<0.01);B组平均收缩压和舒张压由(155.0±12.9)mm Hg和(90.9±10.1)mm Hg分别降至(128.6±9.9)mm Hg和(77.7±9.0)mm Hg(均为P<0.01)。治疗前和治疗后及两组之间比较,治疗方案对baPWV、心率、血脂、血糖和肌酐无明显影响。B组治疗后尿酸水平由治疗前的(335.8±58.5)μmol/L上升到(361.4±51.3)μmol/L(P=0.017)。结论两种联合治疗方案均有良好的降压作用,对baPWV均无显著影响。     

Prior antihypertensive treatment and admission blood pressure correlated with clinical outcome and early morning presentation in hypertensive ischaemic stroke patients

Blood pressure (BP) reduction of 5-6 mm Hg reduces the relative risk of stroke by 30-40%. This effect does not appear to depend on the antihypertensive agent used to bring about the required reduction in BP. Patients with acute ischaemic stroke often exhibit an elevated BP. These patients, who previously suffered from hypertension, have significantly higher levels of BP readings on admission with increased incidence of stroke immediately after arising. The aim of this study was to compare antihypertensive agents, especially short and long acting drugs with the measurement of BP on admission, the time of the ischaemic stroke and its clinical severity. This was studied retrospectively in 109 patients (55 females and 54 males). The mean age was 69.7 +/- 10.4 years. All the patients admitted between 1 July 1996 and 30 June 1997 for ischaemic stroke as established by brain CT scan, were studied. Of the stroke subjects not treated or treated with short acting calcium blockers, 40.8% and 44.4% of them respectively appeared to have an ischaemic stroke in the early morning hours in contrast to 20% of those treated with long acting calcium blockers (P < 0.05). The last group of patients also experienced less clinical severity. These results emphasise the need for proper 24-h control of BP and by comparison to other antihypertensive agents, the long acting calcium blockers with these subjects may prevent a sudden early morning rise in BP, which is instrumental in stroke prevention.     

Cardiac dimensions in spontaneously hypertensive rats following different modes of blood pressure reduction by antihypertensive treatment

The present study examined changes in left ventricular design in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats in response to different types of antihypertensive therapy. Blood pressure was reduced for 12 weeks by either peripheral vasodilators [hydralazine or felodipine (calcium antagonist)] or by sympatholytic drugs (alpha-methyldopa or metoprolol). End diastolic volumes (EDV) were obtained in vitro by determining the diastolic pressure-volume relationships of isolated perfused hearts, arrested in diastole by excluding calcium from the perfusate. Wall thickness (w) and internal radius (ri) were calculated from a ventricle considered as a spherical model. Compared with WKY, untreated SHR had elevated EDV and w. Vasodilator therapy, particularly felodipine, increased EDV but reduced w, while sympatholytic therapy with alpha-methyldopa reduced EDV in SHR. It is suggested that cardiac design is affected not only by the prevailing arterial pressure level which will affect w, but also by the haemodynamic situation. Vasodilators turn such a situation into one characterized by increased cardiac output and hence increased cardiac filling, whereas sympatholytic drugs by venodilatation will turn the haemodynamic situation towards a state characterized by reduced cardiac filling. Left ventricular EDV (ri) therefore seems to adapt to long-term filling conditions, while w adapts to bring w:ri ratio in balance with the pressure load.     

Blood pressure, antihypertensive treatment and factors associated with good blood pressure control in hypertensive diabetics: the Tarmidas study

Numerous population studies confirm the high prevalence of hypertension in type II diabetic (DM2) subjects and that intensive antihypertensive treatment is more beneficial to diabetic than to nondiabetic hypertensive subjects, yet not many of these are specific to Spain. To assess the degree of blood pressure (BP) control and the effects of antihypertensive drugs in the medical management of hypertension in diabetic patients in specialist care centres throughout Spain, we studied the socio-demographic, clinical and relevant laboratory parameters of 796 hypertensive patients with DM2 (mean age 66.09 (95% confidence interval (CI): 64.08-68.10). The percentage of diabetic patients responding positively to BP control measures was lower when compared to the nondiabetic population in both Spain and Europe. The degree of control was poorer for systolic than for diastolic BP, yet 40.6% of the patients were only on monotherapy. The fact that antihypertensive treatment was modified in only 40% of the poorly controlled patients was also highly significant and could be attributed to a nonstringent use of clinical guidelines. Among the other differences between well-controlled and poorly controlled patients, we found that well-controlled patients presented with lower levels of cholesterol and triglycerides, a lower prevalence of excess weight/obesity, and a greater prevalence of cardiovascular and/or cerebrovascular disease despite having a greater percentage of patients on antiplatelet therapy. Better application of therapeutic guidelines and the prevention and treatment of compounding factors could improve the response rate to BP control measures in poorly controlled patients.     

Quality of life of patients receiving antihypertensive treatment

Ninety-four hypertensive patients, 52 females and 42 males, 38 to 79 years old, were investigated for quality of life under antihypertensive treatment, using a self-administered questionnaire. Their social situation, work and leisure activities and hypertension-related symptoms were evaluated when first diagnosed and after treatment with antihypertensive drugs. Of the 94 patients, 85 (90%) felt uneasiness due to hypertension, 21 (22%) felt their work was limited, and 27 (29%) reported restricted leisure activities due to hypertension. Eighteen patients (19%) had sexual problems. Females who were severely hypertensive at first visit (mean BP greater than or equal to 120 mmHg), those who were well-controlled by treatment (mean BP at last visit less than 105 mmHg), and those whose mean BP decreased markedly (decrease in mean BP greater than or equal to 20 mmHg) showed significant improvement in hypertension-related symptoms. Side effects varied depending on the antihypertensive drug used. It is recommended that the quality of life of patients be taken into consideration when choosing antihypertensive drugs.     

Parathyroid hormone-related protein overexpression decreases blood pressure in spontaneously hypertensive rats

We have recently demonstrated that arterial PTHrP expression and cardiovascular responses to this protein are altered in SHR compared with normotensive animals, Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats. To investigate whether the slightly, but significantly decreased, aortic PTHrP gene expression observed in SHR, compared to that of normotensive animals, may play a causative role in the maintenance of the elevated arterial blood pressure (ABP) of the SHR, we transfected a hepatic lobe with a PTHrP expression vector in a sense and antisense orientation. At 24 and 48 hours, sense pSV2neo-ECE induced a significant five-fold increase in PTHrP mRNA abundance with respect to antisense pSV2neo-ECE and vehicle. This increment in the PTHrP mRNA induced by the sense PTHrP expression vector was totally inhibited by the co-administration of the antisense PTHrP expression vector. At the same time, we observed a significant decrease of mean ABP (MABP) in SHR transfected with the sense pSV2neo-ECE to similar values as those obtained in the normotensive strain. Neither antisense PTHrP expression vector nor vehicle had any significant effect in any strain. Again, the effect of the sense PTHrP expression vector on MABP was blocked by the simultaneous treatment with the antisense PTHrP expression vector. At 48 hours, the hypotensive effect of the sense pSV2neo-ECE in SHR was reverted by the i.v. bolus injection of a specific competitive PTHrP receptor antagonist such as Nle8,18,Tyr34-bPTH(3-34)amide. We propose that a defect of this potent local vasodilator may contribute to the development and/or maintenance of arterial hypertension in SHR. This defect can be ameliorated by transfecting tissues with protein-exporting capabilities, such as the liver. Finally, our work adds additional data to a cumulative body of evidence suggesting that it might be possible to design an effective gene therapy to treat the common polygenic and multifactorial form of hypertension by increasing the activity of potent and physiological vasodilators.     

Selective angiotensin receptor antagonism with valsartan decreases arterial stiffness independently of blood pressure lowering in hypertensive patients.

Angiotensin II plays a key role in the development of vascular disease. We examined the long-term effects of selective angiotensin II receptor (ATR) blockade with valsartan on arterial wall stiffness. Brachial to ankle pulse wave velocity (baPWV) was measured in 28 women and 25 men with hypertension (mean age: 62+/-2 years). The measurements were repeated after 24 weeks of treatment with valsartan, 40 to 160 mg/day, with (n=10) or without (n=36) concomitant statin therapy. By multiple regression analysis, baseline baPWV was correlated with age (p<0.001), systolic blood pressure (SBP, p<0.0001), body mass index (p=0.018), and pulse pressure (p=0.005), but not with total cholesterol (p=0.446). Valsartan lowered mean SBP and diastolic blood pressure (DBP) from 155+/-3 to 140+/-3 mmHg and from 90+/-2 to 82+/-2 mmHg, respectively, and mean baPWV from 1,853+/-49 to 1,682+/-52 cm/s. Lowering of baPWV was not influenced by statin therapy. An overlap analysis was performed to separate the effect of angiotensin II receptor blockade from that of blood pressure (BP) lowering. The decrease in the baPWV value of 1,794+/-46 cm/s before valsartan (n=39) vs. 1,663+/-45 cm/s during valsartan (p=0.048, n=31) at a similar mean SBP level (149+/-2 vs. 146+/-3 mmHg, p=0.304) confirmed that ATR blockade had a beneficial effect independent of BP lowering. SBP strongly influences baPWV. However, the decrease in baPWV with valsartan was independent of BP lowering. Statins had no synergistic effect on baPWV. Lowering of baPWV may account for the therapeutic benefit conferred by valsartan independent of its BP-lowering effect.     

Nocturnal blood pressure monitored by ambulatory blood pressure measurement in elderly hypertensive patients.

This study was designed to characterize the nocturnal fall of blood pressure (NFBP) of elderly hypertensive patients (EH), with or without cerebrovascular disease or diabetes mellitus, as measured by automated blood pressure (BP) monitoring. Systolic and diastolic BP and heart rate was measured every 15 minutes in 133 hospitalized patients with nearly similar schedules and diets. The patients were divided into five groups: I, normotensive elderly patients over age 65: II, EH without cardiovascular diseases, controlled without medication: III, EH with cerebral infarction, chronic stage: IV, EH with noninsulin-dependent diabetes mellitus: and V, hypertensives under age 65, without cardiovascular diseases. A significant NFBP was observed in the patients of groups I and V, a significant but smaller NFBP in the hypertensives of groups II and IV, and no NFBP in the patients of group III. Administration of the antihypertensive drugs, enalapril and nifedipine, tended to augment the NFBP. These preliminary observations showed that NFBP did occur in elderly hypertensives but the fall was smaller than that observed in younger hypertensives or elderly normotensives. Although the ambulatory BP measurements were useful in the overall clinical evaluation of elderly patients, NFBP in elderly patients was affected by hypertensive drugs and therefore NFBP should be interpreted with caution.     

Pravastatin affects blood pressure and vascular reactivity

Summary To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10mg/kg per day) was administered orally for 2 or 4 weeks to spontaneously hypertensive rats (SHR/lzm) and normotensive Wistar-Kyoto (WKY/lzm) rats. Blood pressure was significantly increased in the pravastatin-treated groups of both strains, occurring in WKY after a longer treatment period than in SHR. The thoracic aortas from SHR and WKY were pretreated with pravastatin (10^–4M). The vascular response to norepinephrine in terms of both contractility and sensitivity, was increased in the pravastatin-treated SHR aorta but not in the WKY aorta. The increased response was not observed in the presence of mevalonate. Acetylcholine-induced vascular relaxation in the aortas from both strains was not affected by pravastatin pretreatment. These results suggest that the vascular response to norepinephrine may be affected by the intracellular cholesterol synthesis pathway.     

Long-term effects of brief antihypertensive treatment on systolic blood pressure and vascular reactivity in young genetically hypertensive rats

Summary Recent studies have shown that angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR) reduces blood pressure into adulthood. This study explored changes in vascular reactivity in adult normotensive (WKY) rats and stroke-prone SHR (SHRSP) receiving the following treatments at 6–10 weeks of age: (a) ACE inhibitor (ramipril); (b) hydralazine/hydrochlorothiazide (hydral/HCTZ); or (c) no treatment. The hypothesis tested was that vascular changes and blood pressure would be reduced in adult SHRSP treated with ramipril during development. At 17 weeks of age, rats were anesthetized and vascular tissue was excised. Isolated experiments in the aorta included characterization of initial phasic and tonic contractions to 0.1 µM angiotensin II (AII). A phenylephrine (PE) concentration-response curve was performed on carotid arteries, and threshold values were determined. All WKY groups showed lower systolic blood pressure (131±4 mmHg) and reduced phasic AII induced contraction (7.4±4.7%) compared with SHRSP (217±4 mmHg; 37.2±4%). Antihypertensive treatment reduced blood pressure (ramipril: 168±2; hydral/HCTZ: 198±6 mmHg) but not phasic AII responses in adult SHRSP; adult WKY rats were unaffected by treatment. Threshold values for PE in carotid arteries were lower in SHRSP than in WKY, indicating increased sensitivity. However, SHRSP treated with ramipril did not demonstrate increased sensitivity to PE. These data support the hypothesis that blood pressure and sensitivity to PE but not contractile responsiveness to AII in adult SHRSP are determined by an AII-sensitive mechanism during development.     

Office blood pressure variability as a predictor of acute myocardial infarction in elderly patients receiving antihypertensive therapy

Larger variability of office blood pressure (BP) was reportedly associated with a higher risk of stroke or mortality from all causes. In the present study, we focused on the relationship of variability of office BP and occurrence of acute myocardial infarction (MI). We registered 139 patients receiving antihypertensive therapy for more than 1 year who experienced first-ever episode of MI at the age of 60 years or over. At least two sex- and age-matched (+/- 5 years) control patients were registered for every MI patient. Average systolic and diastolic BP during the 12-month period prior to the occurrence of MI, or the time of registration in the case of control patients, was similar in both patient groups. The office BP variability was evaluated by calculating the variation coefficient (VC) of BP. VC of diastolic BP was significantly higher in the MI patients (10.0 +/- 4.0%) compared with the control patients (8.8 +/- 3.4%). VC of systolic BP was not different between the MI and the control patients. Multiple logistic analysis revealed the relationship of the VC for office diastolic BP to the occurrence of MI was significant after adjustment for BP level, age, gender, body mass index, serum total cholesterol concentrations, diabetes mellitus, and current smoking. In conclusion, larger long-term variability of office diastolic BP during antihypertensive therapy is a predictor of MI.     

Pharmacogenomics of blood pressure response to antihypertensive treatment

PURPOSE IDENTIFICATION: Inter-individual variability in blood pressure response to treatment is well documented, but a clinically useful means to distinguish responders from non-responders has been elusive. With the advent of new technologies and genomic knowledge, more investigators are seeking to identify genetic determinants of blood pressure response to therapy. STUDY SELECTION: We identified studies of candidate polymorphisms from an initial PubMed search using the MESH terms 'Hypertension: Drug Therapy' and 'Genetics' or 'Pharmacogenetics', limiting results to English-language publications on studies in human adults. We further identified specific polymorphisms of interest noted in earlier reviews and performed additional PubMed searches based on these candidate genes. Pertinent studies were further extracted from the references of studies already identified. We focused on clinical trials that measured blood pressure response to a medication or class of medications over a minimum of 4 weeks. DATA EXTRACTION: We evaluated studies looking at blood pressure response to commonly used classes of antihypertensive medications by major genetic variants. RESULTS OF ANALYSIS: Although many studies show that blood pressure response to a given class of antihypertensive medications varies by genotype for different polymorphisms, none of the genotypes identified consistently predicted blood pressure response. CONCLUSIONS: Common variants may influence response to diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, but studies of polymorphisms have generally yielded conflicting results. The inclusion of pharmacogenomic studies in large clinical trials and other more innovative investigative methods may provide greater clarity of the potential role for genotyping in the treatment of patients with hypertension.