Non-dipping pattern relates to endothelial dysfunction in patients with uncontrolled resistant hypertension

Resistant hypertension (RHTN) includes both patients whose blood pressure (BP) is uncontrolled on three or more medications (uncontrolled RHTN (UCRH)) and patients whose BP is controlled with use of four or more drugs (controlled RHTN (CRH)). It is unknown whether endothelial function and nocturnal drop demonstrate a similar pattern in patients with CRH and UCRH. We examined circadian BP patterns and vascular function in these patients. In all, 40 CRH and 26 UCRH patients, and 25 normotensives underwent biochemical testing, ambulatory BP monitoring, determination of brachial artery responses to endothelial-dependent (flow-mediated; dilation (FMD)) and independent (nitroglycerin mediated) stimuli. The nighttime drop in systolic BP (SBP) and diastolic BP (DBP) was less pronounced in UCRH than in CRH (SBP, 1.9±1.6 versus 4.9±1.7%; DBP, 7.5±1.8 versus 10.9±1.8%, UCRH and CRH, respectively; P<0.05). FMD was greater in control group compared with RHTN patients. Patients with UCRH had significantly impaired FMD compared with CRH (5.9±2.3% versus 7.1±5.1%; P<0.0001). Therefore, UCRH patients have less nocturnal dipping and a more impaired endothelial response compared with CRH patients. These findings suggest that important differences among patients with RHTN may allow identify subgroups with increased cardiovascular risk.     

A titrate-to-goal study of switching patients uncontrolled on antihypertensive monotherapy to fixed-dose combinations of amlodipine and olmesartan medoxomil ± hydrochlorothiazide

In the prospective, open-label, titrate-to-goal Blood Pressure Control in All Subgroups With Hypertension (BP-CRUSH) study, 999 patients with hypertension uncontrolled on monotherapy (mean age, 55.6 ± 11.4 years; baseline blood pressure [BP], 153.7 ± 9.2/91.9 ± 8.6 mm Hg) were switched to fixed-dose amlodipine/olmesartan medoxomil (AML/OM) 5/20 mg. Patients were uptitrated every 4 weeks to AML/OM 5/40 mg and 10/40 mg to achieve BP < 120/70 mm Hg. Patients were subsequently uptitrated every 4 weeks to AML/OM+hydrochlorothiazide (HCTZ) 10/40+12.5 mg and 10/40+25 mg to achieve BP <125/75 mm Hg. The primary end point, the cumulative percentage of patients achieving seated systolic BP < 140 mm Hg (< 130 mm Hg for patients with diabetes) by week 12, was 75.8%. The mean (± standard error) BP changes from baseline during the titration periods ranged from -14.2±0.4 mm Hg/-7.7 ± 0.3 mm Hg for AML/OM 5/20 mg to -25.1 ± 0.7 mm Hg/-13.7 ± 0.4 mm Hg for AML/OM+HCTZ 10/40+25 mg. By week 20, the cumulative BP threshold of <140/90 mm Hg was achieved by 90.3% of patients. An ambulatory BP monitoring substudy (n=243) showed that 24-hour efficacy was maintained. Treatment-emergent adverse events (TEAEs), mostly mild to moderate in severity, occurred in 529 patients (53.0%). Drug-related TEAEs occurred in 255 patients (25.5%). This well-tolerated, treat-to-goal algorithm enabled a large proportion of patients with uncontrolled hypertension on monotherapy to safely achieve BP control on single-pill AML/OM combination therapy or triple therapy with the addition of HCTZ. .     

Characteristics of resistant hypertension: ageing, body mass index, hyperaldosteronism, cardiac hypertrophy and vascular stiffness

Resistant hypertension (RHTN) includes patients whose blood pressure (BP) is controlled with the use of four or more antihypertensive medications, and is referred to as 'controlled resistant hypertension' (CRH). While specifically comparing patients with CRH and uncontrolled resistant hypertension (UCRH), we hoped to identify distinguishing characteristics that would provide insight into factors contributing to resistance to antihypertensive therapies. RHTN patients were identified as controlled (CRH, n=43) or uncontrolled (UCRH, n=47). No statistical differences were observed between the CRH and UCRH subgroups with respect to age and gender. The body mass index, aldosterone-renin ratio and pulse wave velocity (PWV) were significantly higher in UCRH patients. Although both subgroups showed increased cardiac mass, left ventricular mass index was significantly higher in UCRH compared with CRH patients. Multivariate linear regression analysis indicated that PWV was significantly dependent on age in both UCRH and CRH patients; however, the influence of ageing was more pronounced in the former subgroup. Older age, greater vascular stiffness, higher aldosterone levels and greater left ventricular hypertrophy were significantly associated with lack of BP control in patients with RHTN. These findings suggest important possibilities in terms of preventing and better treating RHTN.     

Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial

Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving ≥3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central α-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (-15±14 mm Hg) were greater than for guanfacine (-12±13 mm Hg; P<0.05) but not greater than placebo (-14±14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (-9±12 mm Hg) more than placebo (-2±12 mm Hg) or guanfacine (-4±12 mm Hg) after 14 weeks of treatment (P<0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points. The results of this trial highlight the importance of ambulatory BP monitoring in the design of hypertension clinical studies.     

Usefulness of exercise-induced hypertension as predictor of chronic hypertension in adults after operative therapy for aortic isthmic coarctation in childhood

Chronic hypertension is a major concern in adults who have undergone resection of coarctation of the aorta (CoA) in childhood. In otherwise healthy subjects, exercise-induced hypertension is prognostic for chronic hypertension; however, the prognostic value in patients with CoA remains unknown. The aim of the present study was to evaluate the predictive value of exercise-induced hypertension for chronic hypertension in these patients. In the present prospective follow-up study, 74 patients with CoA (58% men, age 30.9 ± 9.5 years) underwent ambulatory blood pressure (BP) monitoring and exercise testing twice from 2001 to 2009 with a follow-up period of 6.3 ± 0.8 years. Hypertension was defined as a mean systolic BP ≥140 mm Hg and/or mean diastolic BP ≥90 mm Hg or the need for antihypertensive treatment. Exercise-induced hypertension was defined as a mean systolic BP of <140 mm Hg and peak exercise systolic BP of ≥200 mm Hg. At baseline, 27 patients (36%) were hypertensive, 11 (15%) had exercise-induced hypertension, and 36 (49%) were normotensive. At follow-up, all 27 hypertensive patients remained hypertensive. Of the 11 with exercise-induced hypertension, 7 (64%) had developed chronic hypertension, and 4 (36%) continued to have exercise-induced hypertension. Of the 36 normotensive patients, 7 (19%) had developed hypertension, 12 (33%) had developed exercise-induced hypertension, and 17 (47%) remained normotensive. On multivariate analysis, baseline maximum exercise systolic BP was independently associated with the mean systolic BP at follow-up (β = 0.13, p = 0.005). In conclusion, the maximum exercise systolic BP was a predictor for chronic hypertension in patients with CoA. These findings demonstrate the clinical importance of exercise-induced hypertension and warrant additional study into the long-term consequences of exercise-induced hypertension and the potential beneficial role of early antihypertensive treatment in adult patients after CoA repair with exercise-induced hypertension.     

Blood pressure telemonitoring is useful to achieve blood pressure control in inadequately treated patients with arterial hypertension

Failing to reach blood pressure (BP) goals is one of the main problems in hypertension management. Especially in high-risk patients, intensive monitoring including frequently office visits or new techniques to monitor home BP is required. A total of 60 patients with uncontrolled hypertension were included and randomized into a group with telemetric BP monitoring (TBPM) (n=30) and a control group receiving standard care (n=30). During the 3-month study period, patients received in addition to their antihypertensive pre-treatment up to 2 × 300?mg irbesartan to achieve the required target BP. All patients were instructed to measure their BP once daily in the morning. In the TBPM group automatic alerts were generated by the central database server using pre-defined algorithms and patients were subsequently contacted by the physician. At baseline mean 24-h ambulant BP monitoring (ABPM) was 143.3±11.1/82.6±9.9?mm?Hg in the TBPM group and 141.4±12.6/82.1±6.5?mm?Hg in the standard care group. During treatment mean systolic BP showed a more intensive decrease in the TBPM vs control group (-17.0±11.1?mm?Hg vs -9.8±13.7?mm?Hg; P=0.032). Patients in the TBPM group had a more pronounced night dipping and a higher reduction of mean pulse pressure than controls (-8.1±5.9?mm?Hg vs -2.8±7.4?mm?Hg, P=0.004). After 3 months, TBPM-treated patients were given a higher mean daily dose of irbesartan (375±187?mg vs 222±147?mg in controls; P=<0.001). We demonstrated that with TBPM a more effective and faster titration of the antihypertensive agent is possible. The alarm criteria chosen were useful to improve BP control.     

Management of hypertension in patients with diabetes using an amlodipine-, olmesartan medoxomil-, and hydrochlorothiazide-based titration regimen

The safety and efficacy of an amlodipine/olmesartan medoxomil (OM)-based titration regimen was assessed in patients with type 2 diabetes mellitus and hypertension. After a 2- to 3-week placebo run-in period, 207 patients received amlodipine 5 mg and were uptitrated to amlodipine/OM 5/20, 5/40, and 10/40 mg and then amlodipine/OM 10/40 mg plus hydrochlorothiazide 12.5 and 25 mg in a step-wise manner at 3-week intervals if the seated blood pressure (BP) remained ≥120/70 mm Hg. The primary end point was the change from baseline in the mean 24-hour ambulatory systolic BP after 12 weeks of treatment. The baseline mean ± SD seated cuff systolic/diastolic BP was 158.8 ± 13.1/89.1 ± 10.1 mm Hg and the mean ± SD 24-hour ambulatory systolic/diastolic BP was 144.4 ± 11.7/81.6 ± 9.8 mm Hg. At week 12, the change from baseline in the mean ± SEM 24-hour ambulatory systolic/diastolic BP was -19.9 ± 0.8/-11.2 ± 0.5 mm Hg (p<0.0001 vs baseline), and 70% of patients had achieved a 24-hour ambulatory BP target of <130/80 mm Hg. At the end of 18 weeks of active treatment in patients uptitrated to amlodipine/OM 10/40 mg plus hydrochlorothiazide 25 mg, the change from baseline in the mean ± SEM seated BP was -28.0 ± 1.5/-13.7 ± 1.0 mm Hg (p<0.0001 vs baseline), with 62% of patients reaching the guideline-recommended seated BP goal of <130/80 mm Hg. Drug-related treatment-emergent adverse events occurred in 19.3% of patients. The most frequent events were peripheral edema (6%), dizziness (3%), and hypotension (2%). In conclusion, this amlodipine/OM-based titration regimen was well tolerated and effectively lowered BP throughout the 24-hour dosing interval in patients with hypertension and type 2 diabetes.     

Aortic blood pressure and arterial stiffness in patients with controlled resistant and non‐resistant hypertension

The purpose of the current study was to determine whether aortic blood pressure (BP) and arterial stiffness are greater in patients with controlled resistant hypertension (RHTN) than controlled non‐resistant hypertension (non‐RHTN) despite similar clinic BP level. Participants were recruited from University of Alabama at Birmingham (UAB) Hypertension Clinic. Controlled hypertension was defined as automated office BP measurement with BP < 135/85 mm Hg. A total of 141 participants were evaluated by pulse wave analysis (PWA) and carotid‐femoral pulse wave velocity (cf‐PWV). Among them, 75 patients had controlled RHTN with use of 4 or more antihypertensive medications and 56 patients had controlled non‐RHTN with use of 3 or less antihypertensive medications. Compared to patients with controlled non‐RHTN, those with controlled RHTN were more likely to be African American and had a higher prevalence of diabetes mellitus and congestive heart failure. The mean number of antihypertensive medications was greater in patients with controlled RHTN (4.4 ± 0.8 vs 2.3 ± 0.7, P < .001). Clinic brachial BP, aortic BP, augmentation pressure (AP), augmentation index normalized for heart rate of 75 beats per minute (AIx@75) and cf‐PWV were similar in both groups. In summary, there was no significant difference in central BP or arterial stiffness between patients with controlled RHTN and controlled non‐RHTN. These findings suggest that the higher residual cardiovascular risk observed in patients with RHTN after achieving BP control compared to patients with more easily controlled hypertension is not likely attributable to persistent differences in central BP and arterial stiffness.     

Resistant hypertension, obstructive sleep apnoea and aldosterone

Obstructive sleep apnoea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is strongly associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure (BP). Determining why OSA is so strongly linked to having hypertension in cross-sectional studies, but yet CPAP therapy has limited BP benefit needs further exploration. The CPAP studies do, however, indicate a wide variation in the BP effects of CPAP, with some patients manifesting a large antihypertensive benefit such that a meaningful BP effect can be anticipated in some individuals. OSA is particularly common in patients with resistant hypertension (RHTN). The reason for this high prevalence of OSA is not fully explained, but data suggest that it may be related to the high occurrence of hyperaldosteronism in patients with RHTN. In patients with RHTN, it has been shown that aldosterone levels correlate with severity of OSA and that blockade of aldosterone reduces the severity of OSA. Overall, these findings are consistent with aldosterone excess contributing to worsening of underlying OSA. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid within the neck, which then contributes to increased upper airway resistance.     

Effects of Spironolactone on Dialysis Patients With Refractory Hypertension: A Randomized Controlled Study

The purpose of this study was to evaluate the effects of spironolactone on dialysis patients with refractory hypertension and possible adverse effects. This was a 12‐week prospective, randomized, double‐blind trial of 82 patients randomly assigned to 12‐week treatment with 25 mg/d spironolactone or placebo as add‐on therapy. Visits were scheduled at the start of treatment and after 12 weeks. Measurements of 24‐hour ambulatory blood pressure (BP) monitoring and morning BP were performed. After 12 weeks, spironolactone significantly improved refractory hypertension. Average placebo‐corrected morning BP was reduced by 16.7/7.6 mm Hg. Mean 24‐hour ambulatory BP was reduced by 10.9/5.8 mm Hg. In contrast, serum aldosterone levels in the spironolactone group slightly increased and serum potassium levels insignificantly increased. This study has demonstrated that spironolactone (50 mg) safely and effectively reduces BP in patients with refractory hypertension undergoing dialysis.     

Effectiveness of the selective aldosterone blocker,eplerenone, in patients with resistant hypertension

Resistant hypertension is defined as uncontrolled hypertension despite intensive treatment with at least three antihypertensive agents, one of which ideally should be a diuretic. To determine the efficacy and safety of the selective aldosterone antagonist eplerenone in this population, we studied patients with resistant hypertension (clinic blood pressure [BP] >140 mm Hg systolic or >90 mm Hg diastolic on maximal doses of more than three antihypertensive agents, including a loop or thiazide diuretic). At baseline and after 12 weeks of eplerenone therapy (50 to 100 mg daily titrated to effect), patients underwent clinic and 24-hour BP measurements, serum potassium, plasma renin activity, and serum aldosterone measurements. Patients (n = 52) completing the trial averaged 62 ± 10 years of age, were overweight (mean body mass index, 32.1 ± 5.5 kg/m²), and had variable renal function (glomerular filtration rate, 106 ± 38 mL/minute); 70% were men and 74% were non-Black. The mean number of antihypertensive agents at baseline was 3.7 ± 0.8 (range, three to seven drugs) to achieve a clinic BP of 150.5/84.1 mm Hg. The mean serum aldosterone was 12.9 ± 7.6 ng/mL and plasma renin activity was 2.3 ± 2.7 ng/mL/hour. After eplerenone, the change from baseline in the clinic BP was −17.6/−7.9 mm Hg (P < .0001 for both systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and in 24-hour BP was −12.2/−6.0 mm Hg (P < .0001 for both). The number of antihypertensive drugs decreased to 3.3 ± 0.9 (range, one to seven agents). Plasma potassium increased by 0.30 ± 0.45 mEq/L (P < .001), but there were only three instances in two patients of mild hyperkalemia (potassium >5.5 mEq/L, but <6.0 mEq/L), despite all patients being on a background therapy that included an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Reductions in clinic and ambulatory BP were related to baseline clinic and ambulatory BP values (r² > 0.3 for both SBP and DBP, P < .0001), weakly related to baseline serum aldosterone (r = −0.30; P = .05), and unrelated to plasma renin activity, age, gender, or race. In conclusion, eplerenone demonstrated substantial efficacy in treatment-resistant hypertension and was well-tolerated with modest changes in plasma potassium. Serum aldosterone and plasma renin activity did not predict BP responses to eplerenone in this population.     

Blood pressure control and physician management of hypertension in hospital hypertension units in Spain

Goal blood pressure (BP) was defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) and the World Health Organization-International Society of Hypertension (WHO/ISH) as <140 mm Hg systolic and <90 mm Hg diastolic for the general and <130 mm Hg systolic and <85 mm Hg diastolic for special high-risk populations. However, there are few reports that address BP control among special subgroups of hypertensives by reference to targeted BP. We therefore conducted a study to evaluate BP control of 4049 hypertensives in 47 hospital-based hypertension units in Spain. Overall, 42% of patients achieved goal BP (<140 mm Hg systolic and <90 mm Hg diastolic). Only 13% of diabetic patients and 17% of those with renal disease achieved the BP goal (<130 mm Hg systolic and <85 mm Hg diastolic), and only 10% and 12%, respectively, achieved the even more rigorous goal (<130 mm Hg systolic and <80 mm Hg diastolic). Likewise, only 18% of patients in JNC-VI risk group C and 17% of WHO/ISH high-risk patients attained a goal BP <130 mm Hg systolic and <85 mm Hg diastolic. BP control (<125 mm Hg systolic and <75 mm Hg diastolic) was extremely low (2%) in patients with proteinuria >1 g/d. Poorer BP control was observed among patients at high risk, with diabetes, renal disease, or obesity, than in lower-risk groups. BP control was lower for systolic than for diastolic BP. In >50% of uncontrolled patients, no measures were taken by doctors to optimize pharmacologic treatment, and approximately one-third of patients were still using drug monotherapy. Control of BP, particularly of systolic BP, is still far from optimal in hospital-based hypertension units. Patients at high risk, with diabetes or proteinuria, warrant focused attention. Moreover, a more aggressive behavior of doctors treating uncontrolled hypertension is needed.     

经皮肾动脉射频消融术对犬高血压影响机制的探讨

目的 实验证明交感神经活性增强与高血压的发生有关,我们研究的旨在探讨去神经术对犬高血压的治疗,并评估其有效性与安全性.方法18只杂种犬随机分为干预组(n=10)和对照组(n=8)两组,制作成高血压模型,干预组给予经皮肾交感神经去神经化治疗,实验对照组仅造成高血压模型,不行干预治疗.观察平均血压的变化,分别在术前和术后2、4、6、10周监测血压,同时在术后第2、6、10周监测血肾素活性、血管紧张素Ⅱ、醛固酮和肌酐等指标,通过对这些数据进行方差分析,来评价手术的有效性与安全性.结果在干预组,造模后平均血压增高明显,从(131.4±18.0)mm Hg(1 mm Hg =0.133 kPa)升至(150.6±18.8)mm Hg(P=0.001);在去神经治疗后,平均血压在2、4、6和10周后分别降至(130.4±14.1)mm Hg、(136.2-17.1)mm Hg、(128.7±14.7)mm Hg和(126.1±12.7)mm Hg.同时肾素活性,血管紧张素Ⅱ、醛固酮水平都较术前下降(P＜0.05),肌酐水平无明显变化(P＞0.05).对照组各项指标均无明显变化.结论交感神经兴奋在高血压的产生和发展过程中发挥着重要的作用,经皮肾动脉射频消融术能够产生显著和持久的血压下降,并且手术过程没有造成严重肾功能受损.     

Plasma renin activity and norepinephrine as predictors for antihypertensive effects of nifedipine and captopril

To examine predictors for the efficacy of antihypertensive agents, we investigated the effects of nifedipine and captopril on blood pressure (BP) and humoral factors in patients with essential hypertension. Eleven essential hypertensive patients (mean age: 54) were treated with long acting nifedipine at 20 to 40 mg/day for 8 weeks and 25 essential hypertensives (mean age: 51) were treated with captopril at 37.5 to 75 mg/day. Blood pressure was measured every 2 weeks. Plasma renin activity (PRA), and plasma concentrations of aldosterone, epinephrine and norepinephrine were determined before and at the end of treatment. Both nifedipine and captopril decreased BP (nifedipine: mean BP 119 +/- 3 to 101 +/- 2 mm Hg, captopril: 124 +/- 2 to 100 +/- 2, P less than .01 for each), whereas neither of them affected heart rate. The 8-week treatment of nifedipine showed no significant effect on humoral factors. Captopril increased PRA by 63% (P less than .05) and decreased plasma epinephrine by 42% (P less than .01) and norepinephrine by 35% (P less than .01). The change in mean BP was positively correlated with pretreatment PRA (r = 0.68, P less than .01) in nifedipine-treated patients and inversely with pretreatment norepinephrine (r = -0.53, P less than .01) in captopril treatment. The results suggest that both nifedipine and captopril were effective antihypertensive agents and that the long term treatment of nifedipine is more effective in essential hypertensives with lower PRA, while captopril is more effective in those with higher plasma norepinephrine concentration.     

Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension

BACKGROUND: Uncontrolled hypertension (UH) may be caused by hyperaldosteronism, and some experts recommend the routine use of aldosterone antagonists in this condition. The purpose of this study was to evaluate the efficacy of this approach and to characterize those who respond effectively to an add-on aldosterone antagonist. METHODS: We retrospectively analyzed the effectiveness of spironolactone, an aldosterone antagonist, used as add-on therapy, compared with a standard add-on treatment, in patients referred to a hypertension clinic with UH despite the use of two or more antihypertensive drugs. RESULTS: A total of 340 patients (186 male) with an average age of 63 +/- 14 years were followed for at least 3 months. Of the patients, 42 received add-on spironolactone and 298 received an additional antihypertensive drug other than spironolactone. Baseline characteristics were similar in both groups. Blood pressure (BP) decreased significantly in both groups. In patients who received spironolactone, BP decreased by 23.2/12.5 mm Hg from 165 +/- 27/94 +/- 15 to 142 +/- 25/81 +/- 9 mm Hg, whereas in patients who received other add-on therapy BP decreased by 7.6/5.8 mm Hg from 160 +/- 24/91 +/- 12 to 152 +/- 20/85 +/- 11 mm Hg (P < .05). Patients who received spironolactone had lower serum potassium levels than those who did not receive spironolactone 3.8 +/- 0.4 v 4.5 +/- 0.5 mmol/L respectively (P < .001). Potassium levels <4 mmol/L were associated with a greater reduction in BP. CONCLUSIONS: Add-on spironolactone is a highly effective add-on treatment in UH, mainly in patients with low serum potassium levels. Further studies assessing serum potassium as a marker for treatment approach are needed to establish the role of aldosterone antagonists in the management of UH.     

Effectiveness of furosemide in uncontrolled hypertension in the elderly: role of renin profiling

BACKGROUND: Despite many advances in the treatment of hypertension, adequate blood pressure (BP) control in elderly patients continues to be a challenge. Optimal control of BP remains elusive because of issues relating to drug dosage and proper choice of therapeutic agents, including questions regarding the role of diuretics. METHODS: We examined the effect of diuretic treatment on BP in 12 elderly hypertensive patients whose hypertension was poorly controlled on previous drug regimens. We also evaluated the relationship of systolic, diastolic, and mean arterial BP (SBP, DBP, MAP, respectively) to changes in plasma renin activity (PRA), serum aldosterone (SA), atrial natriuretic peptide (ANP), and serum chemistries both before and after adding furosemide to the prior antihypertensive agents. RESULTS: At baseline, 83% of patients had low PRA (< 1 ng/mL/h). After furosemide, in 67% of patients, decreases in SBP (166 +/- 5 to 134 +/- 5 mm Hg; P <.001), DBP (82 +/- 4 to 71 +/- 4 mm Hg; P =.004), and MAP (111 +/- 3 to 92 +/- 3 mm Hg; P <.001), were associated with increases in PRA (2.1 +/- 1.2 to 5.1 +/- 1.8 ng/mL/h; P =.01) and SA (4.8 +/- 1.0 to 9.4 +/- 1.4 ng/dL; P =.01) and with decreases in ANP (101 +/- 28 to 58 +/- 11 pg/mL; P =.01) and body weight (77.5 +/- 3.6 to 76.4 +/- 3.3 kg; P =.02), findings consistent with volume mediated/salt sensitive hypertension. In the remaining 33% of patients, BP also decreased significantly, but there was no increase in PRA (0.15 +/- 0.05 to 0.10 +/- 0 ng/mL/h) or SA (9.2 +/- 2.2 to 7.0 +/- 0.8 ng/dL) and no decrease in ANP (66 +/- 5 to 75 +/- 18 pg/mL) (P = ns for all), suggesting alternate mechanisms for their responses. CONCLUSIONS: Many of the elderly hypertensive patients in our study had decreased PRA levels and showed significant reductions in BP after furosemide administration. Despite the associated increases in PRA and SA and decreases in ANP in 67% of patients, diuretic use remains important in the control of hypertension in this population.     

Improving Blood Pressure Control: Increase the Dose of Diuretic or Switch to a Fixed‐Dose Angiotensin Receptor Blocker/Diuretic? The Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect (Val‐DICTATE) Trial

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.     

Adverse cardiac remodeling is absent in patients with true controlled resistant hypertension

Resistant hypertension (RHTN), defined as blood pressure (BP) that is uncontrolled with ≥3 medications, including a long-acting thiazide diuretic, also includes a subset with BP that is controlled with ≥4 medications, so-called controlled RHTN. This resistance is attributed to intravascular volume excess. Patients with RHTN overall have a higher prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction compared to patients with non-RHTN. We tested the hypothesis that patients with controlled RHTN due to the intravascular volume excess have higher left ventricular mass index (LVMI), higher prevalence of LVH, larger intracardiac volumes, and more diastolic dysfunction compared to patients with controlled non-resistant hypertension (CHTN), defined as BP controlled with ≤3 anti-hypertensive medications. Patients with controlled RHTN (n = 69) or CHTN (n = 63) who were treated at the University of Alabama at Birmingham were offered enrollment and underwent cardiac magnetic resonance imaging. Diastolic function was assessed by peak filling rate, time needed in diastole to recover 80% of stroke volume, E:A ratios and left atrial volume. LVMI was higher in patients with controlled RHTN (64.4 ± 22.5 vs 56.9 ± 11.5; P = .017). Intracardiac volumes were similar in both groups. Diastolic function parameters were not significantly different between groups. There were no significant differences in age, gender, race, body mass index, dyslipidemia between the two groups. The findings show that patients with controlled RHTN have higher LVMI, but comparable diastolic function to those of patients with CHTN.     

Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment

Hypertension is a very common modifiable risk factor for cardiovascular morbidity and mortality. Patients with hypertension represent a diverse group. In addition to those with primary hypertension, there are patients whose hypertension is attributable to secondary causes, those with resistant hypertension, and patients who present with a hypertensive crisis. Secondary causes of hypertension account for less than 10% of cases of elevated blood pressure (BP), and screening for these causes is warranted if clinically indicated. Patients with resistant hypertension, whose BP remains uncontrolled in spite of use of 3 or more antihypertensive agents, are at increased cardiovascular risk compared with the general hypertensive population. After potentially correctible causes of uncontrolled BP (pseudoresistance, secondary causes, and intake of interfering substances) are eliminated, patients with true resistant hypertension are managed by encouraging therapeutic lifestyle changes and optimizing the antihypertensive regimen, whereby the clinician ensures that the medications are prescribed at optimal doses using drugs with complementary mechanisms of action, while adding an appropriate diuretic if there are no contraindications. Mineralocorticoid receptor antagonists are formidable add-on agents to the antihypertensive regimen, usually as a fourth drug, and are effective in reducing BP even in patients without biochemical evidence of aldosterone excess. In the setting of a hypertensive crisis, the BP has to be reduced within hours in the case of a hypertensive emergency (elevated BP with evidence of target organ damage) using parenteral agents, and within a few days if there is hypertensive urgency, using oral antihypertensive agents.     

Improvement of coronary microvascular function after Angiotensin receptor blocker treatment with irbesartan in patients with systemic hypertension

Patients with hypertension exhibit changes in vessel conductance and resistance. The aim of this study was to evaluate the effect of the angiotensin receptor blocker irbesartan on coronary microvascular function. Thirty-six hypertensive patients without coronary artery or systemic disease were examined. Coronary flow velocity reserve (CFR) was measured using transthoracic Doppler echocardiography in 18 men (54±9 years) before and after 3 months of treatment with 600 mg/d of irbesartan and in 18 controls (55±11 years). Carotid intima-media thickness (IMT) was evaluated with high-resolution echocardiography. Baseline CFR did not differ between groups. CFR significantly improved in the irbesartan group (from 2.87±.42 to 3.78±.32; P<.001), but remained unchanged in controls (from 2.94±.61 to 3.06±.72; P=not significant). CFR improved with treatment independent of associated risk factors. BP decreased from 150±18 mm Hg to 129±25 mm Hg (P<.001) during treatment, whereas IMT and left ventricular mass index showed no significant differences at the end of the follow-up period in both groups. Three-month irbesartan treatment significantly increased CFR in patients with hypertension. This improvement is attributed to blockade of the renin-angiotensin system. Coronary microvascular function was shown to improve independent of hypertrophy regression. Patients with lower baseline CFR tended to show a more pronounced CFR response.