Addition of spironolactone in patients with resistant hypertension: A meta-analysis of randomized controlled trials

This study was designed to assess the effect of additional spironolactone on blood pressure in patients with resistant hypertension. MEDLINE, EMBASE, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that determined the effect of add-on spironolactone on blood pressure in patients with resistant hypertension compared with a control group. A total of five RCTs met the inclusion criteria. Spironolactone reduced office systolic blood pressure (SBP) by 15.73 mmHg (95% CI ?20.45 to ?11.0; P < 0.00001) and office diastolic blood pressure (DBP) by 6.21 mmHg (95% CI ?8.33 to ?4.1, P < 0.00001) as compared to placebo group. The pooled changes of 24 h ambulatory or home SBP and DBP were ?8.7 mmHg (95% CI ?8.79 to ?8.62, P < 0.00001) and ?4.12 mmHg (95% CI ?4.48 to ?3.75, P < 0.00001), in favor of the spironolactone group. In comparison with alternative drugs including beta-blocker, candesartan, or alpha methyldopa, spironolactone reduced home SBP by 4.5 mmHg (95% CI ?4.63 to ?4.37, P < 0.00001). Addition of spironolactone provides benefit effect on blood pressure in patients with resistant hypertension.     

ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.

The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and /=140 and /=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.     

Predictors of the Short-Term Effect of Isoleucine–Proline–Proline/Valine–Proline–Proline Lactotripeptides from Casein on Office and Ambulatory Blood Pressure in Subjects with Pharmacologically Untreated High-Normal Blood Pressure or First-Degree Hypertension

Our aim was to evaluate the predictors of Isoleucine–Proline–Proline/Valine–Proline–Proline (IPP–VPP) lactotripeptides (LTPs) antihypertensive effect in the context of a short-term large double-blind randomized clinical trial involving 164 pharmacologically untreated subjects in primary prevention for cardiovascular disease. When compared with the baseline, office systolic blood pressure (SBP) (?3.42 mm Hg, P < .001) and diastolic blood pressure (DBP) (?2.35 mm Hg, P < .001) significantly decreased, in the LTP-treated patients only. No significant change in predictors during the study of ambulatory blood pressure measurement (ABPM) parameters was observed. A short-term supplementation with LTPs significantly improves the office SBP and DBP, especially in male subjects. The main predictor of LTP antihypertensive effect was the baseline BP.     

他汀类药物对高血压患者降压效应的Meta分析

目的 评价他汀类药物对高血压患者的降压效应.方法 在PubMed、Embase和Cochrane library中检索2012年12月31日之前的所有关于他汀类药物与高血压相关的随机对照试验,按照纳入与排除标准纳入合格文献,采用改良Jadad量表对纳入文献进行质量评价.两位作者独立从文本和表格中提取干预组和对照组治疗前后的收缩压和舒张压值及样本量.运用Review manager 5.0软件分析加权均数差及95%可信区间.结果 符合纳入标准的文献有33篇,共计2915例患者.与对照组相比,他汀类药物治疗组收缩压下降1.52 mmHg[95%可信区间（CI）：-2.35～-0.68,P=0.0004],舒张压下降1.02 mmHg（95%CI：-1.70～-0.34,P=0.003）.若基线血压≥140/90 mmHg,他汀类药物组收缩压下降 2.28 mmHg（95%CI：-3.57～-1.00,P=0.0005）,舒张压下降1.87 mmHg（95%CI：-3.12～-0.62,P=0.003）;基线收缩压＜140/90 mmHg,他汀类药物对血压的影响不明显（P均＞0.05）.在不同他汀类药物的亚组分析中,阿托伐他汀可使收缩压下降4.04 mmHg （95%CI：-6.43～-1.65,P=0.00009）,舒张压下降2.67 mmHg（95%CI：-4.32～-1.02,P=0.002）,其他他汀类药物对血压的影响不明显（P均＞0.05）.他汀类药物治疗（3～6）个月时降压效果最明显.结论 他汀类药物可降低高血压患者的收缩压和舒张压,且与基线血压相关,当基线血压高于140/90 mmHg时降压效应显著,以阿托伐他汀的降压效应最为明显,且治疗3～6个月时效果明显.     

Orthostatic function after renal sympathetic denervation in patients with resistant hypertension

Introduction

Catheter-based renal denervation (RDN) reduces local and whole-body sympathetic activity and blood pressure (BP) in patients with resistant hypertension. However, safety concerns exist concerning the development of orthostatic dysfunction after RDN.

Methods and results

In 36 patients (65 ± 7.6 years, 75% male) with resistant hypertension (office BP 162 ± 24/91 ± 14 mm Hg) treated with 4.8 ± 1.7 antihypertensive drugs, tilt table testing (TTT) was performed before and three months after RDN. Response to RDN was defined as a reduction in office systolic BP (SBP) ≥ 10 mm Hg three months after RDN. Responders (n = 26; 72.2%) and non-responders (n = 10; 27.8%) were evaluated separately. After RDN, office SBP and diastolic BP (DBP) were reduced by 29 ± 6.2/14 ± 3.6 mm Hg (p < 0.0001; p = 0.0002) only in responders. During TTT, SBP and DBP in supine position were only reduced in responders. Resting heart rate (HR) decreased in responders but not in non-responders by 5.9 ± 1.7 beats/min (p = 0.0016). Mean and minimal SBP were not altered during passive tilting. In the responder group, ?SBP was reduced in the initial phase of tilting. The adaptive increase of HR was preserved in both groups after RDN, while only in responders mean and minimal HR were reduced after passive tilting. Following drug provocation, mean and minimal SBP during all phases of passive tilting remained unchanged. ?SBP, ?HR and total number of (pre-)syncopes were neither influenced by RDN nor differing between responders and non-responders.

Conclusions

In patients with resistant hypertension, RDN reduced office BP, supine BP and HR during TTT without causing orthostatic dysfunction or (pre-)syncopes three months after treatment.     

Potential impact of systematic and random errors in blood pressure measurement on the prevalence of high office blood pressure in the United States

The authors examined the proportion of US adults that would have their high blood pressure (BP) status changed if systolic BP (SBP) and diastolic BP (DBP) were measured with systematic bias and/or random error versus following a standardized protocol. Data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES; n = 5176) were analyzed. BP was measured up to three times using a mercury sphygmomanometer by a trained physician following a standardized protocol and averaged. High BP was defined as SBP ≥130 mm Hg or DBP ≥80 mm Hg. Among US adults not taking antihypertensive medication, 32.0% (95%CI: 29.6%,34.4%) had high BP. If SBP and DBP were measured with systematic bias, 5 mm Hg for SBP and 3.5 mm Hg for DBP higher and lower than in NHANES, the proportion with high BP was estimated to be 44.4% (95%CI: 42.6%,46.2%) and 21.9% (95%CI 19.5%,24.4%). Among US adults taking antihypertensive medication, 60.6% (95%CI: 57.2%,63.9%) had high BP. If SBP and DBP were measured 5 and 3.5 mm Hg higher and lower than in NHANES, the proportion with high BP was estimated to be 71.8% (95%CI: 68.3%,75.0%) and 48.4% (95%CI: 44.6%,52.2%), respectively. If BP was measured with random error, with standard deviations of 15 mm Hg for SBP and 7 mm Hg for DBP, 21.4% (95%CI: 19.8%,23.0%) of US adults not taking antihypertensive medication and 20.5% (95%CI: 17.7%,23.3%) taking antihypertensive medication had their high BP status re‐categorized. In conclusions, measuring BP with systematic or random errors may result in the misclassification of high BP for a substantial proportion of US adults.     

Evaluation of Blood Pressure Reduction Response and Responder Characteristics to Fixed‐Dose Combination Treatment of Amlodipine and Losartan: A Post Hoc Analysis of Pooled Clinical Trials

Data from four clinical trials compared reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among patients treated with amlodipine/losartan 5/50 mg vs 5/100 mg and amlodipine/losartan 5/50 mg vs amlodipine 5 mg and 10 mg. Response rate was assessed as reduction in SBP or DBP (>20/10 mm Hg) and proportion of patients achieving SBP <140 mm Hg or DBP <90 mm Hg. Patients were grouped into quartiles based on baseline SBP and DBP. Mean SBP and DBP were reduced in amlodipine/losartan 5/50 mg (n=182) and amlodipine/losartan 5/100 mg (n=95) users across all baseline quartiles. Patients using amlodipine/losartan 5/50 mg had significantly greater SBP and DBP reductions vs amlodipine 5 mg (P=.001 and P=.02, respectively). Amlodipine/losartan 5/50 mg users had significantly greater SBP reduction vs amlodipine 10 mg (SBP P=.02; DBP P=not significant). The odds of responding to therapy were significantly greater with amlodipine/losartan 5/50 mg vs amlodipine 5 mg (odds ratio, 5.33; 95% confidence interval, 1.42–25.5) and were similar vs amlodipine 10 mg (odds ratio, 0.67; 95% confidence interval, 0.017–9.51). These results support the use of combination therapy early in the treatment of hypertension.     

罗格列酮在老年2型糖尿病患者中的降压与内皮保护作用

目的 观察胰岛素增敏剂罗格列酮对老年2型糖尿病患者的降压作用及其对血管内皮的保护作用.方法 将104例无高血压史(未服用降压相关药物)的老年2型糖尿病患者按初诊收缩压(SBP)分为3组,理想血压组(SBP≤120 mm Hg,1 mm Hg=0.133 kPa)42例,例,前期高血压组(140mm Hg≥SBP>120 mm Hg)33例,轻度高血压组(160 mm Hg≥SBP>140 mm Hg)29例.维持原治疗不变,应用岁格列酮4 mg/d,治疗12周.测定治疗前、后SBP、舒张压(DBP)、空腹血糖(FBG)、糖化血红蛋白(Hb)Alc、稳态模型评估一胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白(LDL)、vWF、白细胞(WBC)计数、C反应蛋白(CRP)、非对称性二甲基精氨酸(ADMA)水平.结果 用药12周后,轻度高血压组治疗后SBP及DBP均较治疗前有所下降,差异有统计学意义(P<0.05).前期高血压组治疗后SBP 下降,有统计学意义(P<0.05),而DBP虽下降,但无统计学意义.3组FBG、HbAlC、HOMA-IR、TC、LDL较治疗前下降,差异有统计学意义(P<0.05).另外,治疗后vWF、WBC及CRP也较治疗前下降,筹异有统计学意义(P<0.05).结论 罗格列酮可以降低老年2型糖尿病患者的SBP及DBP,对于基础血压高者降压效果更为显著,同时还可改善内皮细胞功能,发挥保护内皮的作用.     

Clinical predictors of the response to short-term thiazide treatment in nondiabetic essential hypertensives

Blood pressure (BP) response to diuretics is varied in hypertensive patients. This study aimed to identify the patients who may respond better or worse to thiazide diuretics. Nondiabetic patients with treated or untreated hypertension were evaluated if they did not take diuretics and their office systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg. Diet and life style modification were advised in addition to the concomitant medication, if there were, for 2 weeks. Additional hydrochlorothiazide 50 mg was given per day for another 2 weeks. Both office and 24-h ambulatory BP were checked. The changes of office SBP were used for the response to thiazide treatment. A total of 92 patients were enrolled. Compared with those in the quartile of worst response, patients in the quartile of best response were older with increased baseline SBP and pulse pressure (PP) and reduced heart rate. Reduced baseline awake, but not increased sleep DBP was associated with better response to thiazide. Besides, baseline age, SBP and PP were correlated to the response to thiazide treatment. Among these variables, increased baseline mean BP independently predicted the best and reduced SBP predicted the worst responders. Accordingly, patients with higher mean BP respond better to thiazide treatment no matter with or without concomitant medication. Patients with mainly diastolic hypertension with lower SBP responded poorly to thiazide treatment. The findings may help to individualized use of thiazide in nondiabetic hypertensives.     

The effects of school‐based lifestyle interventions on body mass index and blood pressure: a multivariate multilevel meta‐analysis of randomized controlled trials

Primary prevention of childhood obesity and related hypertension is warrant given that both risk factors are intertwined and track into adulthood. This systematic review and meta‐analysis assess the impact of school‐based lifestyle interventions on children's body mass index (BMI) and blood pressure. We searched databases and prior reviews. Eligibility criteria were the following: randomized controlled trial design, evaluation of a school‐based intervention, targeting children aged 4–12 years, reporting on BMI and/or related cardiovascular risk factors, reporting data on at least one follow‐up moment. The effects on BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated by means of univariate and multivariate three‐level random effects models. A total of 85 RCTs (91 papers) were included in the meta‐analyses. In univariate models, the pooled effects were ?0.072 (95%CI: ?0.106; ?0.038) for BMI, ?0.183 (95%CI: ?0.288; ?0.078) for SBP and ?0.071 (95%CI: ?0.185; 0.044) for DBP. In multivariate analyses, the pooled effects of interventions were ?0.054 (95%CI: ?0.131; 0.022) for BMI, ?0.182 (95%CI: ?0.266; ?0.098) for SBP and ?0.144 (95%CI: ?0.230; ?0.057) for DBP. Parental involvement accentuated the beneficial effects of interventions. School‐based lifestyle prevention interventions result in beneficial changes in children's BMI and blood pressure, and the effects on the latter may be stronger than and accrue independently from those in the former.     

LCZ696, a First‐in‐Class Angiotensin Receptor‐Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension

The safety of LCZ696, a novel angiotensin receptor‐neprilysin inhibitor, was evaluated for the first time in patients with severe hypertension in this 8‐week, multicenter, open‐label study. Thirty‐five Japanese patients with either office systolic blood pressure (SBP) ≥180 mm Hg or diastolic blood pressure (DBP) ≥110 mm Hg received LCZ696 200 mg. If blood pressure was uncontrolled, the LCZ696 dose was increased to 400 mg after 2 weeks (if there were no safety concerns; n=32), followed by an optional addition of another antihypertensive drug (except angiotensin receptor blocker and angiotensin‐converting enzyme inhibitor) after 4 weeks (n=21). Reductions in office SBP/DBP (baseline, 173.4 mm Hg/112.4 mm Hg) and pulse pressure (baseline, 61.0 mm Hg) at week 8 were 35.3/22.1 mm Hg and 13.2 mm Hg, respectively. The overall incidence of adverse events was 48.6% with no reports of dizziness, hypotension, or angioedema. The LCZ696‐based regimen was generally well‐tolerated and could present a treatment option for severe hypertension in Asian patients especially in reducing SBP and pulse pressure.     

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.     

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was ?1.6 mm Hg (?4.2, 1.1), ?1.1 mm Hg (?3.9, 1.6), and ?4.9 (?7.5, ?2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (?6.7 mm Hg [?10.5, ?2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.     

Evaluation of the potential interaction between NaCl and prostaglandin inhibition in elderly individuals with isolated systolic hypertension.

OBJECTIVE: To evaluate whether prostaglandin inhibition with the non-steroidal anti-inflammatory drug (NSAID), indomethacin (I) interacts synergistically with different doses of salt (NaCl) in elevating systolic blood pressure (SBP). DESIGN AND METHODS: This randomized, placebo-controlled, double-blind, crossover study examined the interaction between NaCl and the prostaglandin inhibitor, I in 31 healthy elderly individuals with a mean age (+/- SD) of 68.7+/-5.7 years (range 61-85 years). Participants aged more than 60 years on a 140 mmol/day NaCl dose for 6 weeks were chosen with normal blood pressure [24-h SBP <148 mm Hg, diastolic blood pressure (DBP) <85 mm Hg on the Takeda Ambulatory Blood Pressure Monitor (TABPM); n = 15] and isolated systolic hypertension (ISH), [24-h SBP >148 mm Hg, 24-h DBP <85 mm Hg on TABPM; n = 16]. Exclusion criteria included uncontrolled hypertension (SBP >220 mm Hg and/or DBP >110 mm Hg), cardiac disease, creatinine clearance <60 ml/min, dementia and recent cerebrovascular accident or secondary hypertension. A 2x2 Latin square design was structured using four treatment groups [low salt (NaCl = 90 mmol/day) + I placebo, high salt (NaCl = 240 mmol/day) + I placebo, low salt + I (25 mg three times daily) and high salt + I] for 2 weeks each, balanced and interspersed with 2 week washout periods to minimize carryover effects. Twenty-four hour SBP, DBP and heart rate were measured and summarized using a moving interval averaging technique. The mean change in 24-h SBP, DBP, heart rate, urinary Na+, K+, protein and creatinine, creatinine clearance and serum electrolytes were compared across treatments in the total cohort and in ISH and control groups separately using ANCOVA (SAS). RESULTS: In the total cohort, compared with low NaCl, chronic high NaCl increased mean SBP (5.76 mm Hg; P = 0.0002) and DBP (3.36 mm Hg; P = 0.002). Indomethacin significantly increased mean SBP (2.66 mm Hg, P = 0.015) but not DBP (0.31 mm Hg, P = 0.419). High salt and I were additive (SBPT, DBPT) but there was no interaction (P = 0.795 and P = 0.739, respectively). Additionally, chronic high NaCl increased serum Na (P = 0.0001) and 24-h urinary Na (P = 0.0001) as expected. Indomethacin significantly decreased mean heart rate (P = 0.018). The effects of NaCl and I on SBP, DBP and heart rate were not modified by age, alcohol intake, serum K+, body mass index or treatment order. In the ISH group, NaCl dose significantly elevated SBP (9.87 mm Hg; P = 0.0001) and DBP (5.26 mm Hg, P = 0.006) but did not significantly alter blood pressure in the normotensive group. Indomethacin significantly elevated SBP (P = 0.03) in normotensive individuals but had no effect on blood pressure in the ISH group. CONCLUSIONS: Chronic high salt diet elevated blood pressure more than I in the total cohort of elderly individuals. No interaction was demonstrated and their effects were additive. In the ISH group, chronic high salt diet significantly increased SBP and DBP while I failed to alter blood pressure. In the normotensive group, I, but not salt, elevated SBP. Patients with ISH are sensitive to the pressor effect of NaCl but resistant to the pressor effect of prostaglandin inhibition in contrast to elderly normotensive control individuals where the reverse was found.     

Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM

This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated.     

Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients. A prospective study in a cohort of naive patients

OBJECTIVES: To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. METHODS: A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) > or =140 mm Hg and/or diastolic BP (DBP) > or =90 mm Hg] was defined according to international criteria. RESULTS: Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. CONCLUSIONS: Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART.     

The relationship between systolic blood pressure and cardiovascular risk--results of the Brisighella Heart Study

We examined the relationship of systolic (SBP) and diastolic (DBP) blood pressure, and pulse pressure to coronary heart disease and cerebrovascular disease risk in a prospective population-based European cohort. The Brisighella Heart Study included 2939 men and women between the ages of 14–84 without prior coronary heart disease or cerebrovascular disease and not taking antihypertensive therapy at baseline. Cox regression was used to obtain hazard ratios (HRs) for coronary heart disease and cerebrovascular disease as a function of baseline blood pressure parameters over a 23-year follow-up. Higher combined coronary heart disease and cerebrovascular disease risk was evident in comparison to the referent of <120 mm Hg, with a 44% increased risk at SBP 120–139 mm Hg (HR, 1.44; 95% confidence interval [CI], 1.00–2.09; p =0.052), 76% increased risk at SBP 140–159 mm Hg (HR, 1.76; 95% CI, 1.16–2.69; p =0.009), and 109% increased risk at SBP ≥160 mm Hg (HR, 2.09; 95% CI, 1.31–3.35; p =0.0021). Trends of increasing risk with increasing levels of blood pressure were significant for SBP and pulse pressure, ( p <0.0001) but not for DBP ( p =0.058). In this European cohort, SBP was a stronger predictor of coronary heart disease and cerebrovascular disease events than DBP, and an increase in risk was already evident with highnormal SBP (120–139 mm Hg). The prognostic significance of pulse pressure was also demonstrated. The importance of SBP as seen in the Framingham Heart Study may be generalized to a European population with differences in diet and other risk factors.     

24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg), valsartan/hydrochlorothiazide (320/25?mg), amlodipine/valsartan (10/320?mg) or amlodipine/hydrochlorothiazide (10/25?mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8?mm?Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8-24.1/11.7-15.5, 19.0-25.1/12.0-16.0 and 18.3-22.6/11.1-14.3?mm?Hg (P≤0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ≤130/85?mm?Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.     

The efficacy and safety of low- and high-dose fixed combinations of irbesartan/hydrochlorothiazide in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial

This multicenter, prospective, open-label, single-arm study determined the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients (n=1005), aged 18 years and older, with uncontrolled systolic blood pressure (SBP) of 140-159 mm Hg (130-159 mm Hg for type 2 diabetes mellitus) after at least 4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Enrolled patients (n=844) were aged 57.3+/-11.2 years; 52% were women, 23% were African American, and 14% were Hispanic. Thirty percent had type 2 diabetes mellitus, 46% had metabolic syndrome, and baseline blood pressure was 154.0+/-10.3/91.3+/-8.8 mm Hg. The mean change in SBP from placebo end to the primary end point, Week 18 (intent-to-treat population, n=736) was -21.5+/-14.3 mm Hg (p<0.001). The mean change in diastolic blood pressure (DBP) was -10.4+/-8.7 mm Hg (p<0.001). The mean Week 18 SBP/DBP was 132.9+/-13.8/81.1+/-9.7 mm Hg. Overall, 77% (95% confidence interval, 74%-80%) of patients achieved SBP goal (<140 mm Hg; <130 mm Hg for type 2 diabetes mellitus); 83% (95% confidence interval, 80%-86%) achieved DBP goal (<90 mm Hg; <80 mm Hg for type 2 diabetes mellitus); and 69% (95% confidence interval, 66%-72%) achieved dual SBP/DBP goal. Treatments were well tolerated. This irbesartan/HCTZ treatment regimen achieved SBP goals in more than 75% of patients uncontrolled on monotherapy.     

Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies

OBJECTIVES: To compare the ability of telmisartan and losartan to reduce mean diastolic blood pressure (DBP) during the last 6 h of the 24-h dosing interval in a prospectively planned meta-analysis of ambulatory blood pressure monitoring (ABPM) data from two independent studies. METHODS: Data were from two independent randomized, double-blind, double-dummy, titration-to-response studies conducted in patients with mild-to-moderate hypertension (seated cuff DBP 95-109 mmHg, 24-h mean ambulatory DBP >or=85 mmHg). After a 4-week placebo run-in period, patients received once-daily telmisartan 40 mg or losartan 50 mg, with up-titration after 4 weeks to telmisartan 80 mg or losartan 100 mg, respectively, if seated trough cuff DBP >or=90 mmHg. Blood pressures were recorded using ABPM immediately before randomization and after 8 weeks of active treatment. In addition, seated trough cuff blood pressures were measured at baseline and after 4 and 8 weeks of active treatment. RESULTS: Titration to the higher dose was required in 60.1% of telmisartan patients and 69.5% of losartan patients (P=0.01). Reductions from baseline in the last 6 h mean ambulatory DBP with telmisartan and losartan were 6.6+/-0.4 and 5.1+/-0.4 mmHg, respectively (P<0.01, adjusted for baseline and study); the effects were homogeneous across the two studies. During the last 6 h of the 24-h dosing interval, telmisartan produced greater reductions in each of the observed hourly mean ambulatory DBP values. Telmisartan-induced reductions were also greater for the majority of the observed hourly mean ambulatory DBP values over the entire 24-h dosing interval. Reductions from baseline in the last 6 h adjusted mean ambulatory systolic blood pressure (SBP) for telmisartan and losartan were 9.9+/-0.6 and 7.8+/-0.6 mmHg, respectively (P=0.01). The 24-h profiles of ambulatory SBP hourly mean reductions were similar to those for DBP. Both telmisartan and losartan were found to be safe and well tolerated. CONCLUSIONS: Telmisartan 40/80 mg is superior to losartan 50/100 mg in controlling DBP and SBP during the last 6 h of the 24-h dosing interval.