Persistence on Treatment and Blood Pressure Control with Different First-Line Antihypertensive Treatments: A Prospective Evaluation

We enrolled 347 hypertensive patients, randomly allocated them to different first-line treatments, and followed-up for 24 months. Persistence on treatment was significantly higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs. CCBs (51.6%), β-blockers (44.8%), and diuretics (34.4%). No ARB, ACE inhibitor, β-blocker, or diuretic was associated with a greater persistence in therapy as compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs. other CCBs (59.3% vs. 46.6%). Systolic and diastolic BP decreased more in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) when compared to ß-blockers (-4.0/-2.3 mmHg) and diuretics (-2.3/-2.1 mmHg).     

Persistence on treatment and blood pressure control with different first-line antihypertensive treatments: a prospective evaluation

We enrolled 347 hypertensive patients, randomly allocated them to different first-line treatments, and followed-up for 24 months. Persistence on treatment was significantly higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs. CCBs (51.6%), beta-blockers (44.8%), and diuretics (34.4%). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a greater persistence in therapy as compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs. other CCBs (59.3% vs. 46.6%). Systolic and diastolic BP decreased more in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) when compared to beta-blockers (-4.0/-2.3 mmHg) and diuretics (-2.3/-2.1 mmHg).     

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.     

Blood pressure control in kidney transplantation: therapeutic implications

Post-transplant hypertension remains a significant risk factor for graft loss, but whether or not specific blood pressure (BP) medications affect graft outcome is still unknown. We assessed the interaction between BP control and antihypertensive drugs on graft outcome. We retrospectively examined clinic BP data for 1662 renal transplant (RTx) patients, transplanted between 1994 and 2000 at our centre. The analysis examined all patients who received central alpha-agonists and peripheral alpha-antagonists, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibition (ACEI), angiotensin receptor blockers (ARBs). BP recordings during treatment were categorized for each agent. Thus, a particular BP could be categorized for multiple medications. A total of 1462 patients (pts) (88%) were Caucasian and 800 pts (46%) received cadaveric RTx. There were 10.6+/-6.8 BP measurements for each patient post-RTx. CCBs, alone among the classes of antihypertensive drugs evaluated, reduced the risk for graft loss (RR: 0.736; P=0.035) in the overall analysis. Interestingly, stratifying levels of BP control unmasked a beneficial effect on graft survival of ACEI/ARB therapy in individuals with higher levels of systolic (>152 mmHg) and diastolic blood pressure (>98 mmHg) treated with ACEI/ARBs compared to individuals treated with CCBs (P<0.01 for each). Thus, stabilizing BP is important post-RTx. CCBs are associated with improved rates of graft survival. Their role in a compromised RTx, however, deserves further study. ACEI/ARBs have clear benefits, improving graft survival in individuals with elevated systolic blood pressure and proteinuria. CCBs are not as efficacious in this setting.     

Renoprotective effect and cost-effectiveness of using benidipine, a calcium channel blocker, to lower the dose of angiotensin receptor blocker in hypertensive patients with albuminuria.

In hypertensive patients with chronic renal disease, angiotensin receptor blockers (ARBs) are among the first-line drugs, and calcium channel blockers (CCBs) are recommended as a second line. We examined the effects of two therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP), urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned randomly to two groups. In Group A (n=14), the ARB dose was maximized and then benidipine was added until BP targets were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first and then the ARB dose was increased until BP targets were reached. The BP targets were achieved by ARB alone in 36% of Group A patients and by the addition of benidipine in 83% of Group B patients. Finally, BP decreased in each group, reaching the targets in 93% of Group A patients and 94% of Group B patients after a 4-month therapeutic period. UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period (-33+/-6% in Group A, -31+/-6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426+/-880 vs. 8,955+/-410 yen, p=0.012) and the cost-effectiveness of antihypertensive treatment was lower (p=0.003) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is, in light of the renal protection and the cost-effectiveness of this approach, a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria.     

Improvement of blood pressure control in hypertensive patients with renal diseases.

For hypertensive patients with renal diseases (RD), strict blood pressure (BP) control has been recommended in recent hypertension guidelines, such as JNC VI, JNC 7, WHO/ISH 1999 and ESH-ESC 2003. We assessed the current status of BP control and the changes of BP control before and after the publication of these guidelines in 489 hypertensive patients with or without RD (age, 19-89 years, mean 59+/-13 years) who visited the hypertension and kidney outpatient clinic at Kyushu University Hospital. The clinical characteristics of RD and non-RD patients were assessed (RD patients: age, 20-89 years, mean 60+/-13 years, n=311; non-RD patients: age, 19-86 years, mean 58+/-13 years, n=178). In addition, we compared the BP control status in 2003 to that in 1996. In 2003, the BP in RD patients was 134+/-16/78+/-10 mmHg and that in non-RD patients was 138+/-12/83+/-9 mmHg. When strict BP control was defined as <130/80 mmHg, the frequency of strict BP control in RD patients was 28.9% in 2003. In addition, the BP levels of RD patients in 2003 were significantly lower than those in 1996 (134+/-16/78+/-10 mmHg vs. 141+/-17/85+/-10 mmHg, p<0.05 for both systolic blood pressure [SBP] and diastolic blood pressure [DBP]), and the frequency of strict BP control in RD patients was higher in 2003 than in 1996 (28.9% vs. 11.8%, p<0.01). The BP levels of non-RD patients in 2003 tended to be lower than those in 1996 (138+/-12/83+/-9 mmHg vs. 141+/-13/85+/-9 mmHg, n.s.). In 2003, angiotensin II receptor blockers (ARBs) were more frequently prescribed to RD patients than to non-RD patients. Furthermore, the use of ARBs was markedly increased in 2003 compared with 1996. In conclusion, in our outpatient clinic, BP levels in hypertensive patients with RD have improved in recent years, and were lower than those in hypertensive patients without RD, which may in part reflect the physicians' awareness of the importance of strict BP control in RD patients, as suggested by several recent hypertension guidelines.     

Clinical efficacy and tolerability of alpha-blocker doxazosin as add-on therapy in patients with hypertension and impaired glucose metabolism

BACKGROUND AND AIM: The aim of this trial was to evaluate the effect of doxazosin as add-on therapy in patients with hypertension not adequately controlled on current antihypertensive therapy, and impaired glucose metabolism. The effect of doxazosin administered as add-on therapy was to be considered significant both from clinical and statistical viewpoints if the proportion of patients with adequate control of blood pressure (BP<130/85 mmHg) would be at least 30% after 16 weeks of combined therapy. METHOD AND RESULTS: It was an open, multicenter phase IV study, lasting 19 weeks: 3-week qualifying/placebo run-in period+16-week dose titration/add on therapy period, involving 264 out-patients (158 m and 106 f; mean age+/-SD: 60.9+/-8.6 years; mean BMI+/-SD: basal 29.5+/-5.1, final 30.2+/-4.6) with blood pressure still >130/85 mmHg in spite of the antihypertensive treatment (ACE inhibitors 44%, AT II antagonists 21%, Ca antagonists 12%, other drugs 8%, polytherapy 15%) and affected by type 2 diabetes (n=219), impaired fasting glucose (IFG; n=16) or impaired glucose tolerance (IGT; n=29). Following a run-in, 3-week qualifying phase during which placebo was added to ongoing antihypertensive treatment, 16-week treatment with doxazosin was added at dosages from 1 up to 8 mg/day. Main outcome measures were: the percentage of patients with blood pressure <130/85 mmHg at the end of treatment; the effects of the combination therapy on glyco-lipidic metabolism: fasting plasma glucose, fasting insulin, glycated hemoglobin, insulin resistance (HOMA-R), plasma lipids; and the effect on the 10-year CHD risk (Framingham equation). RESULTS: 35% of patients were responsive (BP<130/85 mmHg) to add-on treatment with doxazosin (CI 90%: 30.3%-40.4%; P<0.05, stat. an. intention to treat). During the run-in phase with placebo, mean SBP/DBP (+/-SD) decreased from 155.6+/-13.2/91.8+/-6.8 mmHg (Week -3) to 151.9+/-12.9/90.1+/-7.2 mmHg (Week -1) and to 151.2+/-11.5/90.1+/-6.9 mmHg (Week 0). During add-on treatment with doxazosin, mean SBP/DBP (+/-SD) further decreased to 144.9+/-15.2/86.3+/-8.3 mmHg (Week 4), 139.7+/-15.3/83.4+/-7.9 mmHg (Week 8), 135.5+/-14.3/81.7+/-7.6 mmHg (Week 12) and 136.4+/-14.5/81.0+/-7.0 mmHg (Week 16). Overall, mean BP changes reached a plateau of about -15 mmHg (SBP) and -9 mmHg (DBP) after 16 weeks of treatment; at each visit the mean decreases from baseline were statistically significant. The following mean values of metabolic parameters were reduced during the study: fasting plasma glucose (-4.1mg/dl; -2.8%), fasting insulin (-2 microU/ml; -12.3%; P<0.05), glycated hemoglobin (-0.12%; -1.7%), HOMA-R (-1.03; -18.2%; P<0.05), total cholesterol (-1.85 mg/dl; -1.1%), LDL cholesterol (-1.35 mg/dl; -0.8%) and triglycerides (-5.64 mg/dl; -2.4%); mean HDL cholesterol increased (+1.79 mg/dl; +3.9%; P<0.01). At the end of study treatment, the percentage of patients with lab values returned within normal ranges, in comparison with basal values, was statistically significant (P<0.05) for the following parameters: fasting plasma glucose (6.3%), fasting insulin (7.5%), LDL cholesterol (6.0%). Ten-year CHD risk (+/-SD) decreased from 16.4+/-7.8% to 13.6+/-7.4% (final vs. basal: -2.87+/-3.9; -17%; P<0.01). Six patients (2.3%) reported 8 adverse drug reactions: dizziness (3), edema (2), headache (2), asthenia (1). In one out of these 6 patients, in whom doxazosin was associated to the ACE inhibitor quinapril, adverse reaction (peripheral edema) led to treatment withdrawal. CONCLUSION: In patients not responsive to antihypertensive treatment and concomitantly affected by impaired glucose metabolism, achievement of target BP was obtained in more than one third of cases after 16-week add-on treatment with doxazosin. Changes in glyco-lipidic parameters and reduction of 10-year CHD risk observed during the study, although of moderate extent, confirm the overall favourable effect of antihypertensive combinations including doxazosin.     

Efficacy of combination antihypertensive therapy with low-dose indapamide: assessment by blood pressure self-monitoring at home

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT1-receptor blocker (ARB), but had an average morning home systolic BP (SBP) > or =135 mmHg or diastolic BP (DBP) > or =85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 +/- 12/87 +/- 9 mmHg to 135 +/- 12/81 +/- 9 mmHg), evening home BP (138 +/- 15/79 +/- 10 mmHg to 126 +/- 12/73 +/- 9 mmHg), and casual BP (145 +/- 21/86 +/- 14 mmHg to 136 +/- 17/81 +/- 13 mmHg). All groups showed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.     

Low-dose and very low-dose spironolactone in combination therapy for essential hypertension: evaluation by self-measurement of blood pressure at home

Low-dose (25 mg) or very low-dose (12.5 mg) spironolactone were added among 86 uncontrolled hypertensive patients who were undergoing monotherapy with calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin AT1-receptor blockers (ARBs). Morning home systolic/diastolic blood pressure (BP) reduction was similar among the CCB (n = 30, -8.2/-2.6 mmHg), ACEI (n = 22, -13.0/-4.7 mmHg), and ARB (n = 34, -11.5/-5.1 mmHg) groups. An increase in serum potassium correlated positively with the decline in morning systolic BP. Even very low-dose (12.5 mg) spironolactone is clinically effective, although serum potassium should be carefully monitored.     

Comparison of valsartan and amlodipine on ambulatory blood pressure variability in hypertensive patients

We tested the hypothesis that calcium channel blockers (CCBs: amlodipine group, n = 38)) are superior to angiotensin receptor blockers (ARBs: valsartan group, n = 38) against ambulatory blood pressure variability (BPV) in untreated Japanese hypertensive patients. Both drugs significantly reduced ambulatory systolic and diastolic BP values. With regard to BPV, standard deviation (SD) in SBP did not change with the administration of either drug, but the ARB significantly increased SD in awake DBP (12 ± 4–14 ± 4 mmHg). The ARB also significantly increased the coefficients of variation (CVs)in awake and 24-h SBP/DBP (all P < 0.05), but amlodipine did not change the CV. CCB significantly reduced the maximum values of awake SBP (193 ± 24–182 ± 27 mmHg, P = 0.02), sleep SBP (156 ± 18–139 ± 14 mmHg, P < 0 .001), and awake and sleep DBP (P < 0.01 in both cases), but the ARB did not change the maximum BP values. In conclusion, a once-daily morning dose of CCB amlodipine was more effective at controlling ambulatory BPV than ARB valsartan, especially in reducing maximum BP levels.     

Different influences on central and peripheral pulse pressure, aortic wave reflections and pulse wave velocity of three different types of antihypertensive drugs.

OBJECTIVE: To evaluate in hypertensive patients (pts) with similar peripheral blood pressure (BP) whether different antihypertensive treatments have different influences on aortic stiffness, aortic central pressures and aortic wave reflections. METHODS: In a cross-over study 41 nondiabetic hypertensives (21 women, age 35-60 yrs) were evaluated after stabilized (> 4 months) antihypertensive treatment and with casual BP between 130/80 and 160/95 mmHg. Patients were divided into 3 groups: Group I--12 pts all medicated with beta-blockers; Group II--14 pts all medicated with calcium channel blockers; Group III--15 pts all medicated with either angiotensin-converting enzyme inhibitors (ACEIs) (n = 8) or angiotensin II receptor blockers (ARBs) (n = 7). We evaluated casual BP and carotid-femoral pulse wave velocity (PWV). Systolic blood pressure (SBP) and pulse pressure (PP), left ventricular ejection duration (LVED), augmentation pressure (delta P) and augmentation index (AI%) in the aorta (a measure of aortic wave reflection), derived using radial and carotid applantation tonometry, were measured. Data are means + SEM. RESULTS: For similar casual peripheral BP values, group III vs. group I showed lower (p < 0.05) values of: aortic stiffness--PWV (10.3 +/- 0.2 vs. 11.2 +/- 0.3 m/s), central PP (48 +/- 2 vs. 55 +/- 2 mmHg), delta TP (11 +/- 3 vs. 21 +/- 3 mmHg), LVED (297 +/- 5 vs. 319 +/- 8 ms), AI% (22 +/- 4 vs. 39 +/- 3%), suggesting reduced vascular tone in the arteries and greater brachial-aortic PP amplification. Data in group II did not differ significantly from the other two groups. CONCLUSIONS: Independently of casual BP values, the three classes of antihypertensive drugs appear to have different influences on aortic stiffness, central pressures and aortic wave reflections, ACEIs or ARBs appearing to exhibit a more favorable profile.     

Improved early-phase insulin response after candesartan treatment in hypertensive patients with impaired glucose tolerance

As the effect of renin-angiotensin system (RAS) blockade on beta-cells in clinical situations remains unclear, new evidence has been presented that angiotensin-converting enzyme (ACE) inhibitors and angiotensin vertical line vertical line receptor blockers (ARBs) may delay or prevent the development of insulin resistance and diabetes through novel mechanisms. This study aimed to determine the effects of ARBs on insulin excretion by beta-cells. Hypertensive patients with impaired glucose tolerance were randomly divided into two groups: group A (n = 6), which received 8 mg/day of oral candesartan for three months, and controls (n = 6). Before and after administration, a 75 g oral glucose tolerance test was conducted to compare various parameters. No significant differences in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, or fasting immunoreactive insulin (IRI) were identified between the groups before administration. After three months, there were no significant changes in BMI, SBP, and DBP for the controls and in BMI and DBP for group A. However, SBP was significantly decreased from 144 +/- 2.6 mmHg to 125 +/- 4.6 mmHg in group A. Insulinogenic index tended to be slightly decreased for controls, but was significantly increased from 0.32 +/- 0.0 to 0.47 +/- 0.1 for group A. No significant changes in HOMA-R were identified in either group. To the best of our knowledge, no previous studies have documented a RAS inhibitor improving early-phase insulin response; thus, the present study may be the first of its kind.     

Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in normotensive and hypertensive elderly subjects

OBJECTIVES: To evaluate salt sensitivity in elderly subjects with different forms of hypertension and controls and to investigate any modulation by genotype DESIGN: Randomized, double-blinded, placebo-controlled latin-square SETTING: Tertiary referral hospital PARTICIPANTS: Community subjects (n = 46) aged > or = 60 years classified as isolated systolic hypertension [ISH; systolic blood pressure (SBP) > or = 160, diastolic blood pressure (DBP) < 90 mmHg, n = 19], diastolic +/- systolic hypertension (SDH; DBP > or = 90 mmHg, n = 10) and normotension (SBP < 160, DBP < 90 mmHg, n = 17). INTERVENTION: Four 14 day treatments, 50, 100, 200 and 300 mmol/day of sodium chloride supplementation interspersed with 14 day washout periods on a salt-restricted diet. MAIN OUTCOME MEASURES: The 24 h blood pressure, heart rate, weight, urinary sodium and creatinine clearance measured during baseline, treatment and washout periods and angiotensinogen (AGT) and angiotensin converting enzyme (ACE) genotypes. RESULTS: For the entire cohort, the mean +/- standard error (SE) of change from baseline in SBP for 50, 100, 200 and 300 mmol/day salt was 7.7+/-2.4, 12.1+/-2.4, 16.6+/-3.0, 18.5+/-2.6 mmHg, respectively. For DBP, the respective changes were: -0.1+/-1.5, 2.4+/-1.6, 3.0+/-1.5, 5.8+/-1.7 mmHg. The increase in SBP among ISH subjects was significantly higher than among subjects in the SDH and normotensive groups (P < 0.05). AGT genotype influenced the effect of salt dose on the change in DBP (P = 0.006) but not SBP (P = 0.7). CONCLUSIONS: In healthy, older subjects, a linear increase in BP occurred with increasing salt dose, it appeared most pronounced in ISH subjects and could be modulated by AGT genotype.     

Arterial stiffness is related to augmented seasonal variation of blood pressure in hypertensive patients

BACKGROUND: Seasonal variation in blood pressure (BP), a usual tendency of both systolic (SBP) and diastolic BP (DBP) to rise during winter in hypertensive patients, may be related to the higher cardiovascular mortality in winter. However, it is not yet clear what factors are relevant to the seasonal BP changes. We hypothesized that arterial stiffness is related to the BP changes between summer and winter. METHODS AND RESULTS: Eighty-five elderly (>55 years) patients with essential hypertension (33 males, 64+/-6.0 years) were enrolled. Seasonal BP profiles over at least 2 years were studied along with arterial stiffness and clinical variables (age, gender, smoking, duration of hypertension, anti-hypertensive medications and body mass index). Both SBP and DBP were significantly higher during winter compared with three other seasons (spring 128+/-10.0/79+/-7.3 mmHg, summer 127+/-9.8/78+/-7.1 mmHg, autumn 127+/-10.3/78+/-8.0 mmHg, winter 136+/-12.5/81+/-7.6 mmHg; SBP changes; p<0.001, DBP changes; p<0.001). There were no significant seasonal differences among spring, summer and autumn. Pulse wave velocity (PWV), a widely used clinical indicator of arterial stiffness was correlated with winter-summer differences in SBP (r = 0.272, p = 0.012), but not in DBP (r = 0.188, p = 0.085). Age, which was correlated with PWV strongly (p<0.001), was not significantly related to the seasonal changes in BP (SBP changes; p = 0.114, DBP changes; p = 0.298). No other clinical variables had significant correlation with seasonal BP changes. Multivariate regression analysis revealed that PWV is the only significant predictor for winter-summer SBP changes. CONCLUSIONS: Our results established a feasible link between arterial stiffness and seasonal BP variation. These findings may partly explain higher cardiovascular risk in patients with increased arterial stiffness.     

Pravastatin decreases blood pressure in hypertensive and hypercholesterolemic patients receiving antihypertensive treatment.

BACKGROUND: Previous studies have suggested that the lipid-lowering agents, statins, may help reduce blood pressure (BP). The goal of the present study was to characterize the effect of pravastatin on BP in hypercholesterolemic and hypertensive patients already receiving antihypertensive drugs. METHODS AND RESULTS: Eighty-two patients with hypercholesterolemia were retrospectively studied before and after 3 months of treatment with pravastatin. Forty-four patients had hypertension (HT group) and were receiving antihypertensive treatment, while the remaining 38 patients were normotensive (NT group). Patients in the HT group were further subdivided into those with uncontrolled or controlled BP. Pravastatin treatment significantly reduced systolic BP (SBP) in the HT group (134+/-16 to 130+/-13 mmHg, p<0.005) but not in the NT group (124+/-10 to 123+/-9 mmHg, p=0.52), despite the fact that treatment significantly reduced low-density lipoprotein cholesterol in both groups (HT group 178+/-27 to 132+/-17 mg/dl, p<0.0001; NT group 169+/-27 to 125+/-21 mg/dl, p<0.0001). Further, pravastatin significantly decreased SBP in the uncontrolled BP group (148+/-7 to 138+/-12 mmHg, p<0.005) but not in the controlled BP group (122+/-10 to 123+/-9 mmHg, p=0.72). CONCLUSION: Concomitant use of statins and antihypertensive drugs could result in improved BP control in hypertensive patients with hypercholesterolemia.     

Demographic characteristics and response to antihypertensive treatment. Study using fixed doses of diltiazem

Since the stepped care approach has been widened to four classes of antihypertensive drugs, demographic considerations enter into the choice of the first line drug. Calcium antagonists have been claimed to be more active in older patients because the average BP decrease after dose titration could be greater in this age group than in younger people. In this study, the response to a fixed dose of diltiazem has been related to different demographic factors. The selected patients have been treated with diltiazem 120 mg b.i.d. in monotherapy for at least 14 days irrespective of their response to a lower dose. There were 231 patients (115 M, 116 F). Their average age was 59 +/- 11 years (24 to 82) and their treatment duration was 44 +/- 27 days. Diltiazem lowered BP from 171 +/- 1/103 +/- 7 mmHg to 156 +/- 1/91 +/- 1 mmHg. The decline in both SBP and DBP with diltiazem was significantly related to their control values (r = 0.31 and 0.28 respectively, p less than 0.0001 for both). Although control SBP was related to age (r = 0.40, p less than 0.0001), its decrease with diltiazem was not. Neither control DBP nor its decrease with diltiazem were related to age. Although the average SBP was higher in patients over 60 years than in younger patients (176 +/- 2 mmHg, n = 124 vs 166 +/- 2 mmHg, n = 107, p less than 0.01), its decrease with diltiazem was not significantly greater (- 16 +/- 2 vs - 15 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal protective effect in hypertensive patients: the high doses of angiotensin II receptor blocker (HARB) study.

Angiotensin receptor blockers (ARBs) are the recommended first-line antihypertensive treatment for managing chronic kidney disease, and strict blood pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan and candesartan are commonly used ARBs in Japan, with maximum permissible doses of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after changeover from the maximum dose of candesartan to the maximum dose of valsartan, in 55 poorly controlled hypertensive patients undergoing candesartan treatment who were unable to achieve optimal BP according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). We measured BP and pulse rate and assessed urinary protein excretion (UPE) before and after changeover. Changeover was associated with decreases in systolic BP and diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/-0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had high urinary protein levels prior to changeover without significant decreases in BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001) and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria.     

Effect of doxazosin GITS on 24-hour blood pressure profile in patients with stage 1 to stage 2 primary hypertension

OBJECTIVE: To investigate the effect of the doxazosin gastrointestinal therapeutic system (GITS) on the 24 h blood pressure (BP) profile by ambulatory blood pressure measurements (ABPM) in patients with stage 1 to stage 2 primary hypertension. METHODS AND RESULTS: Seventeen hypertensive patients-either untreated or after a two-week run-in/washout period-underwent office and ABPM monitoring before and six weeks after an open-label once-daily morning dose of 4 mg of doxazosin GITS, an alpha(1)-adrenoceptor antagonist. Fourteen patients responded; three did not. Data analyses refers to the responders: linear analysis demonstrated statistically significant reductions from baseline in daytime, night-time, and total 24 h means for systolic BP (SBP) (7-10 mmHg) and diastolic BP (DBP) (5-10 mmHg) after treatment, with no statistically significant change in heart rate (HR). Rhythm analysis demonstrated statistically significant reductions from baseline in mean mesor (8 mmHg), maximum (6 mmHg) and minimum (10 mmHg) values in SBP, and in mean mesor (5 mmHg), maximum (7 mmHg) and minimum (5 mmHg) values in DBP. Circadian rhythm parameters in BP and HR were not significantly altered by treatment. Treatment with doxazosin GITS was well tolerated. CONCLUSIONS: A single morning dose of doxazosin GITS at 4 mg significantly reduced ambulatory SBP and DBP throughout a 24 h period while preserving a normal 24 h BP and HR rhythm profile in stage 1 to stage 2 hypertensives.