| Background Few studies compared the relative efficacy and tolerability of antihypertensive drug classes as initial treatment for hypertensive patients in rural area in developing countries. The study "An antihypertensive intervention trial to lower blood pressure in untreated hypertensive patients based on the gene polymorphisms in the pathway of the drug-metabolism and biological effects" was a randomized, double-blind, active-controlled, community based clinical trial in rural area in China aiming to determine antihypertensive effects and side effects of Atenolol, Captopril, Nifidipine sustained release (SR) and Hydrochlorothiazide relative to the gene polymorphisms in untreated hypertensive patients in countryside. The present study is the prelementary results of the study to compare the efficacy and tolerability of monotherapy with different classes drugs as initial treatment in untreated patients after 4-week's treatment.Methods At baseline, unrelated patients never receiving antihypertensive therapy aged 40 to 75 years of either sex were recruited from 7 communities in XinYang County from March to May in 2005. A total of 3408 untreated patients (66% women) enrolled with mean systolic blood pressure, 160.5±19.2mmHg; mean diastolic blood pressure, 95.9±11.0mmHg. Patients were randomized to 1 of 4 treatments—Atenolol (25mg/d) group of 594, or Hydrochlorothiazide (25mg/d) of 891, or Nifedipine SR (20mg/d) of 947, or Captopril (50mg/d) of 976,—in a ratio of 1:1.5:1.5:1.5, respectively. The antihypertensive goals were that systolic blood pressure was reduced to less than 140mmHg, or diastolic blood pressure, less than 90mmHg, and the goal-achieving rate from baseline to week 4. Tolerability was assessed by recording adverse events and physical examination.Results On week 4, the goal-achieving rates were 44.5% for systolic pressure and 56.2% for diastolic pressure, respectively. The mean reductions in systolic and diastolic blood pressure were 18.0±21.5mmHg and 8.73±11.2mmHg, respectively. The goal- achieving rates for systolic blood pressure were significantly different among four treatment groups in male (32.7% in Atenolol, 51.9% in Hydrochlorothiazide, 52.2% in Nifedipine SR, and 37.4% in Captopril, respectively, P＜0.001) as well as in female patients (43.3%, 51.7%, 51.8%, and 32.7%, respectively, P＜0.001). After adjustment for the age, blood glucose, drug doses and pretreatment blood pressure, the mean reduction in systolic pressure showed significant difference among 4 treatment groups either in male (11.2±1.5mmHg for Atenolol, 18.7±1.2mmHg for Hydrochlorothiazide, 20.9±1.3mmHg for Nifedipine SR, and 15.7±1.1mmHg for Captopril, respectively, P＜0.001) or in female patients. The mean diastolic pressure showed the similar pattern as systolic pressure with the lowest reduction and goal-achivement rate in Captopril group either in meles or in females. Total adverse event was significantly lower in Hydrochlorothiazide treatment (4.62%) than other treatments (11.1% in Atenolol, 8.03% in Nifedipine SR, and 7.52% in Captopril, respectively; P＜0.001). Discontinuation rate due to adverse events was 2.0% for Hydrochlorothiazide, 6.9% for Atenolol, 5.4% for Nifedipine SR, and 2.8% for Captopril (P＜0.001).Conclusions Our results support that hydrochlorothiazide is suitable as the first line antihypertensive drug in developing countries due to its significantly higher efficacy, better tolerability, and lower cost. Its long-term metabolic side effects and cardiovascular events are under investigation. Background ACE2 is a newer member of renin-angiotensin system. Both ACE2 and ACE are involved in the production of biologically active peptides and appear to have complementary functions in the regulation of blood pressure. We hypothesized ACE2 genetic variations could confer high risk of hypertension and predict blood pressure response to ACE inhibitors.Methods Two case control studies were performed to test the association of single nucleotide polymorphisms of ACE2 and ACE I/D with hypertension (first, 973 cases vs 969 controls; second, 286 cases vs 316 controls). A total of 3,408 untreated hypertensive patients were randomized to captopril, atenolol, hydrochlorothiazide, or nifedipine sustained release treatments for 4 weeks to determine the association of blood pressure response with polymorphisms of ACE2. Five single nucleotide polymorphisms of ACE2 and ACE insert/delete were selected.Results We found an independent association of ACE2 rs2106809 T allele with an increased risk of hypertension in women (OR, 1.59, 95%CI, 1.13 to 2.06, P＜0.001). The genotypes of ACE DD and ACE2 CT/TT had much higher risk of hypertension than did ACE2 CT/TT genotype alone(OR 2.34, 95%CI 1.75 to 4.85, P=0.002). The results were confirmed in the second sample. ACE2 T allele female carriers had 3.3mmHg lower reduction in diastolic blood pressure response to captopril than did CC genotype female carriers after adjusting for pretreatment blood pressure, age, body mass index, and ACE I/D polymorphism (P=0.019). The difference between CC and CT+TT genotype groups was larger in captopril group than other drugs aggregated group in women.Conclusions ACE2 T allele confers high risk of hypertension and can predict blood pressure responses to ACE inhibitors in women.
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