Efficacy of different drug classes used to initiate antihypertensive treatment in black subjects: results of a randomized trial in Johannesburg, South Africa.

BACKGROUND: Thiazides are recommended to initiate antihypertensive drug treatment in black subjects. OBJECTIVE: To test the efficacy of this recommendation in a South African black cohort. METHODS: Men and women (N = 409), aged 18 to 70 years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg, were randomized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained-release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5 mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line drugs were titrated up and after 2 months other medications were added to the regimen. RESULTS: While receiving monotherapy (2 months, n = 366), the patients' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide, and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients treated with nifedipine was controlled: 133 (63.3%, P

Alpha-adducin polymorphism in hypertensives of South African ancestry.

The alpha-adducin gene contributes significantly to hypertension in MHS rats (rats of the Milan hypertensive strain) and in some white and Japanese populations, causing a low renin, sodium, and diuretic-sensitive hypertension. No data are available from populations of African ancestry who have a high prevalence of low renin, sodium, and diuretic-sensitive hypertension. We studied the relationship between the 460-Trp variant of alpha-adducin gene with hypertension using a case-control study design in black South Africans. Surprisingly we found that the overall frequency of the 460-Trp allele was low (approximately 6%), but in spite of such relatively low frequency, the 460-Trp allele was 2.5-fold more frequent in hypertensives than normotensives (P = .028), with an odds ratio for hypertension associated to the state of carrier of at least one 460-Trp allele of 2.68. The finding of such low frequency of the 460-Trp allele in individuals of African ancestry points to the substantial ethnic variability of the genes that have been found to be associated with hypertension. On the other hand, it suggests an association of the 460-Trp allele with hypertension also in subjects of African origin.

Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension.

In this study, using 24-hour ambulatory blood pressure (BP) monitoring, the authors assessed the potential for BP control using hydrochlorothiazide (HCTZ, 12.5 mg daily), given as a monotherapy over 12 months to 49 black South African patients with mild to moderate hypertension (mean day diastolic blood pressure [DBP] > or = 90 and < 115 mmHg). Uncontrolled patients received fixed combination of quinapril/HCTZ 10/12.5, 20/12.5, and 20/25 mg, with dose titration at 3 monthly intervals if BP control was not achieved (day DBP < 90 mmHg). Overall, profound and sustained BP reduction was observed at the end of the study. The 24-hour BP decreased from 151 +/- 14/98 +/- 7 to 136 +/- 15/87 +/- 9 mmHg (p < 0.0001 at end of study vs. baseline); the mean day BP decreased from 155 +/- 14/104 +/- 7 to 140 +/- 15/91 +/- 10 mmHg (p < 0.0001 at end of study vs. baseline). The overall control (mean day DBP < 90 mmHg) and response (decrease in day DBP > or = 10 mmHg) rates were 49% and 61%, respectively. At the end of the study, only 2 patients (4%) remained on treatment with HCTZ. Out of the initial 12 patients controlled on HCTZ at 3 months (12/49, 24%), 5 patients remained controlled at 6 months and only 1 patient at 12 months. In contrast, quinapril/HCTZ combinations maintained their antihypertensive effect up to 9 months, with a significant number of patients (22/49, 45%) requiring the highest dose of the combination (20/25 mg daily). In conclusion, low-dose HCTZ should not be recommended as monotherapy in black patients with mild to moderate hypertension due to the fact that the BP-lowering effect is attenuated already at 6 months of treatment, with most patients requiring the addition of the ACE inhibitor.

Association analysis of beta2 adrenoceptor polymorphisms with hypertension in a Black African population.

OBJECTIVE: To determine whether or not beta2 adrenoceptor polymorphism is a risk factor for the development of hypertension in a Black South African population. BACKGROUND: Attenuated vasodilator responses to endogenous catecholamines may contribute to the aetiology of hypertension. Downregulation of beta2 adrenoreceptors (beta2AR) following stimulation with agonists is determined in part by variation at the beta2AR gene locus. The Glu27 beta2AR genotype results in attenuated downregulation compared with the wild-type Gln27 receptor, whereas Gly16 exhibits enhanced down-regulation compared to Arg16. Possible racial differences in the prevalence of the beta2AR polymorphisms may be an explanation for the blunted responses to isoprenaline and the increased prevalence of hypertension in Black African populations. METHODS: One hundred and ninety-two unrelated hypertensives and 123 normotensives of Black South African origin were studied. Hypertensives were recruited from hospital hypertension clinics in the province of Gauteng and if on treatment, had a 2-4 week washout period before 24-h ambulatory blood pressure assessment Normotensive controls were recruited from the same community. RESULTS: There was no significant association between either the Arg-Gly16 polymorphism or the Gln-Glu27 polymorphism and hypertension status. Furthermore, in the hypertensives, no significant association was seen between beta2AR genotype at either site and clinical blood pressure, 24-h blood pressure or left ventricular mass. A significant association was seen between Arg16 homozygotes and lower body mass index in hypertensives (P = 0.007) although this was not a primary end point. Interestingly, the Glu27 polymorphism was much rarer in this population (allelic frequency 17%) compared to a Caucasian population. CONCLUSION: These data suggest that beta2AR polymorphism is not a risk factor for hypertension per se in this defined population. The possibility that the decreased prevalence of Glu27 in black South African populations explains blunted vasodilator responses to isoprenaline requires further study.

Comparison of acebutolol with and without hydrochlorothiazide versus carvedilol with and without hydrochlorothiazide in black patients with mild to moderate systemic hypertension.

In the present study, we assessed the antihypertensive efficacy of acebutolol 200 mg versus carvedilol 25 mg once daily, given as monotherapy for 3 months to 40 black patients (20 patients in each group, mean age 53+/-10 years, 24 women) with mean blood pressure (BP) during the day >90 and <110 mm Hg. Patients in whom blood pressure could not be controlled took medication, which was increased at 3-month intervals as follows: step 2, acebutolol 200 mg or carvedilol 25 mg plus hydrochlorothiazide 12.5 mg once daily; step 3, acebutolol 400 mg or carvedilol 50 mg plus hydrochlorothiazide 25 mg once daily. Overall, significant but modest BP reduction was achieved with both beta blockers at 3 months. In the acebutolol group, 24-hour BP decreased from 142+/-15/94+/-7 mm Hg to 138+/-16/89+/-8 mm Hg (p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 145+/-15/98+/-5 mm Hg to 140+/-14/93+/-7 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs. baseline). In the carvedilol group, 24-hour BP decreased from 145+/-11/93+/-6 to 138+/-16/87+/-9 mm Hg (p<0.05 for systolic BP and p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 149+/-10/99+/-5 to 141+/-16/91+/-87 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs baseline). At 12 months, most patients required combination therapy to achieve BP control. The control (mean day diastolic BP <90 mm Hg) and response (mean day diastolic BP decrease > or =10 mm Hg) rates at 12 months were 59% and 82% in the acebutolol and 78% and 78% in the carvedilol groups, respectively. In conclusion, acebutolol or carvedilol in combination with hydrochlorothiazide, rather than acebutolol or carvedilol alone, should be considered as first-line antihypertensive therapy in black patients with mild to moderate hypertension.

Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension.

A single-center, prospective double-blind randomized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation (CC), titrated from 10 mg to 40 mg daily, with the angiotensin converting enzyme inhibitor enalapril, titrated from 10 to 40 mg daily, in the treatment of black South African patients with severe hypertension (sitting diastolic blood pressure [DBP] between 115 and 140 mm Hg, confirmed by 24-h ambulatory blood pressure monitoring). Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment. This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily. Ninety-six patients had complete data at baseline, and at the end of the double-blind and open phases, and were included in this analysis. In both groups, all patients required titration up to the maximal dose of double-blind medication. Monotherapy with nisoldipine CC, but not enalapril, significantly reduced both sitting and 24-h ambulatory blood pressure (BP). Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg (P < .0001) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group (P = ns). The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [LV] mass index, observed after only 2 months of treatment (from 146+/-40 to 129+/-35 g/m2, P = .05). In contrast, enalapril had no effect on LV mass (from 139+/-36 to 142+/-50 g/m2, P = NS). The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase, during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg (at baseline) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase (P < .0001). This effect was sustained with trough-to-peak ratio of 74% for systolic and 67% for diastolic BP, with further regression in LV mass. Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC. The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated. The incidence of significant ventricular arrhythmia was also low and did not change with treatment. In conclusion, our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension, based on its profound and sustained blood-pressure-lowering effect, associated with significant regression of left ventricular mass and its low side effect profile.

Once-daily fixed dose combinations of verapamil and trandolapril in black patients with mild to moderate hypertension: a new choice for first line treatment.

Using ambulatory blood pressure (BP) monitoring, a potent ACE-inhibitor/calcium channel blocker combination was tested in 21 Black patients (age 52 +/- 10 years; 10 males, 11 females) with mild to moderate hypertension (mean 12-hour daytime diastolic BP > or = 90 mmHg and < or = 114 mmHg). After a 14-day wash-out and a 14-day placebo run-in period, therapy was initiated with verapamil 180 mg plus trandolapril 2 mg. At monthly visits, if mean daytime diastolic BP remained > or = 90 mmHg, the dose combination was uptitrated stepwise to verapamil 240 mg plus trandolapril 4 mg, verapamil 360 mg plus trandolapril 4 mg, and finally hydrochlorothiazide 12.5 mg were added. Mean 24-hour BP dropped from 150 +/- 14/96 +/- 7 mmHg at baseline to 131 +/- 13/82 +/- 8 mmHg after 4 months treatment (p < 0.001). In 16 (76%) patients mean 24-hour diastolic BP was < 90 mmHg at the end of the trial and 15 (71%) patients achieved a reduction of > 10 mmHg. Five out of 5 patients finishing on dose I were controlled, 5/6 patients on dose II, 5/8 patients on dose III, and 1/2 patients who received additional hydrochlorothiazide. The 24-hour BP load fell from 72 +/- 8% at baseline to 35 +/- 25% in 4 months (p < 0.001). Mean diastolic BP drop for the 2 peak hours during daytime was 20 mmHg and for the last 2 hours of monitoring was 13 mmHg, resulting in a trough to peak ratio of 65%. There were no significant adverse events or biochemical abnormalities. It is concluded that the combination doses tested showed a sustained and marked antihypertensive effect throughout the 24-hour dosing interval, and the starting dose (verapamil 180 mg plus trandolapril 2 mg) seems appropriate in this group of patients.

Repeated automated versus daytime ambulatory blood pressure measurement in mild, moderate and severe untreated black hypertensive patients.

OBJECTIVE: To examine the extent to which one session of repeated automated (30-45 min) blood pressure measurements in non-treated, hypertensive patients can be used to predict daytime ambulatory blood pressure (ABP). METHODS: Two hundred untreated black hypertensive patients (mean age 50.2+/-11.2) were retrospectively stratified on the basis of the daytime ambulatory diastolic blood pressure (DBP) into mild, moderate and severe hypertensives (90 mmHg