Predictors of antihypertensive response to a standard dose of hydrochlorothiazide for essential hypertension.
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BACKGROUND: Determinants of inter-individual variation in blood pressure (BP) response to antihypertensive therapy remain largely unknown. Although differences in race, age and measures of the renin-angiotensin-aldosterone system (RAAS) have been associated with variation in blood pressure response to hydrochlorothiazide, whether these characteristics make additive contributions to predicting response has not been established. We conducted a comprehensive search for predictors of BP response to a standard dose of hydrochlorothiazide in a biracial sample to estimate how much inter-individual variation in BP response could be explained by all of the identified predictors. METHODS: After withdrawal of antihypertensive medications for at least four weeks (baseline) and stabilization on a diet approximating 150 mmol sodium per day, 225 African American and 280 Caucasian subjects with diagnosed essential hypertension were treated for four weeks with hydrochlorothiazide 25 mg per day. At baseline and the end of treatment, subjects were admitted to the General Clinical Research Center for measurement of activity of the RAAS and other regulators of BP. Characteristics measured at study enrollment, at baseline, and in response to drug treatment were incorporated stepwise into linear regression models in order to quantify their additive contributions to predicting BP responses to hydrochlorothiazide. RESULTS: Black race and female gender were both associated with significantly greater systolic (SBP) and diastolic (DBP) blood pressure responses to hydrochlorothiazide. Together the combined effects of race and gender accounted for 11% inter-individual variation in SBP response (P < 0.0001) and 4% of inter-individual variation in DBP response (P < 0.0001). Additional statistically significant predictors of greater systolic and diastolic responses to hydrochlorothiazide included, shorter duration of diagnosed or treated hypertension (P < 0.001), higher baseline BP level (P < 0.0001), lower baseline plasma renin activity (P < 0.05), lower baseline urinary aldosterone excretion (P < 0.002), and greater decrease in urinary sodium excretion (P < or = 0.004). Greater decrease in weight was an additional statistically significant predictor of SBP but not DBP response, and older age was a predictor of diastolic but not SBP response. The combined effects of all identified predictors accounted for 38% of inter-individual variation in SBP response (P < 0.0001) and 20% of inter-individual variation in DBP response (P < 0.0001). CONCLUSIONS: A systematic search reveals numerous predictors of BP response to a standard antihypertensive dose of hydrochlorothiazide. However, because the majority of inter-individual variation in SBP and DBP responses remains unexplained, there is considerable opportunity for future investigations to improve the ability to predict individual BP responses to antihypertensive drug therapy. (+info)
Relationship between treatment-induced changes in left ventricular mass and blood pressure in black african hypertensive patients: results of the Baragwanath Trial.
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BACKGROUND: In a single-center study, we compared to what extent changes in conventional and ambulatory blood pressure (BP) predicted regression of left ventricular mass (LVM) index in response to antihypertensive treatment in previously untreated and treated patients with sustained hypertension. METHODS AND RESULTS: We enrolled 173 black African patients who, off treatment, had a daytime diastolic BP ranging from 90 to 114 mm Hg. Antihypertensive drugs were titrated and combined to reduce the daytime diastolic BP below 90 mm Hg. Echocardiograms were obtained at baseline and follow-up. Mean systolic/diastolic clinic BP, 24-hour BP, and LVM index were similar in previously untreated (n=64) and previously treated (n=109) patients and averaged 171/102 mm Hg, 151/97 mm Hg, and 118 g/m2, respectively. At 4 months, these values had decreased (P<0.001) by 26/12 mm Hg, 23/14 mm Hg, and 14 g/m2 in previously untreated patients and by 22/9 mm Hg, 21/13 mm Hg, and 19 g/m2 in previously treated patients. In the previously untreated patients, the regression in LVM index correlated to a similar degree (P=0.09) with the decreases in the conventional (r=0.34; P=0.005) and the 24-hour (r=0.26; P=0.04) systolic BP. In the previously treated patients, the corresponding correlations were 0.02 (P=0.82) and -0.10 (P=0.32), respectively. Compared with the 24-hour systolic BP, automated oscillometric measurements of systolic BP obtained at the clinic yielded similar results. CONCLUSIONS: In previously untreated patients with sustained hypertension followed at a single center, reductions in clinic and ambulatory systolic pressure in response to antihypertensive treatment equally predicted the regression in LVM index. (+info)
Determination of hydrochlorothiazide, triamterene and propranolol hydrochloride by the spectrophotometric method and high-performance liquid chromatography (HPLC).
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Spectrophotometric and chromatographic (HPLC) methods for determination of hydrochlorothiazide, triamterene and propranolol hydrochloride were elaborated. Both methods were appropriate for the determination of three compounds in pharmaceutical preparations containing their mixtures. Both the elaborated methods for the determination of the studied compounds give comparable results and can successfully be applied to the assay in their mixtures occurring in the composition of pharmaceutical preparations. (+info)
alpha-Adducin 460Trp allele is associated with erythrocyte Na transport rate in North Sardinian primary hypertensives.
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Erythrocyte membrane alterations mirror those of vascular smooth muscle and renal tubular cell membrane. The interaction between adducin and Na-K pump is the most likely biochemical mechanism responsible for the increased tubular Na reabsorption and hypertension in Milan hypertensive strain (MHS) rats. To substantiate this hypothesis in humans, we tested to see if alpha-adducin Gly460Trp genotype is associated with erythrocyte sodium transport rate in a new cohort of n=268 never-treated North Sardinian primary hypertensives. Plasma renin activity and blood pressure response to hydrochlorothiazide were also measured to evaluate the relationship between sodium transport rate and two intermediate phenotypes with a higher degree of genetic complexity. Na-K pump, Na-K-Cl cotransport, and Li-Na countertransport at V(max) were faster (P<0.0001), whereas intracellular Na concentration was lower (P<0.0001) in patients carrying one or two 460Trp alleles. Such behavior was mirrored by opposite changes of intracellular Na concentration. Plasma renin activity and blood pressure response to diuretic treatment, on the other hand, showed a weaker association with the sodium transport rate. In conclusion, our findings are consistent with the hypothesis that the Gly460Trp alpha-adducin polymorphism may affect renal Na handling through an alteration in ion transport across the cell membrane mirrored by erythrocytes. These results may also have clinical relevance because the Gly460Trp alpha-adducin polymorphism may explain, at least in part, the variability of blood pressure response to diuretics in primary hypertensive patients. (+info)
Monitoring one-year compliance to antihypertension medication in the Seychelles.
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OBJECTIVE: To examine the compliance to medication among newly diagnosed hypertensive patients screened from the general population of the Seychelles, a rapidly developing country. METHODS: Among the 1067 participants to a population-based survey for cardiovascular risk factors, hypertension was discovered in 50 (previously unaware of having hypertension and having blood pressure > or = 160/95 mmHg over 3 visits). These 50 patients were placed on a daily one-pill regimen of medication (bendrofluazide, atenolol, or a combination of hydrochlorothiazide and atenolol) and compliance to the regimen was assessed over 12 months using electronic pill containers. Satisfactory compliance was defined as taking the medication on 6 or 7 days a week on average (which corresponds to a mean compliance level of > or = 86%). FINDINGS: In the first month, fewer than half (46%) of the new hypertension patients achieved satisfactory compliance, and only about one-quarter (26%) achieved this level by the twelfth month. Compliance was better among the 23 participants who regularly attended medical follow-up, with nearly three-quarters of these patients (74%) achieving satisfactory compliance during the first month and over one-half (55%) by the twelfth month. There was a direct association between mean 12-month compliance level and having a highly skilled occupation; having good health awareness; and regularly attending medical appointments. In contrast, there was an inverse relationship between mean compliance level and heavy drinking. CONCLUSION: The low proportion of people selected from the general population who were capable of sustaining satisfactory compliance to antihypertension medication may correspond to the maximum effectiveness of medication interventions based on a screening and treatment strategy in the general population. The results stress the need for both high-risk and population approaches to improve hypertension control. (+info)
Efficacy of eprosartan in combination with HCTZ in patients with essential hypertension.
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This randomised, double-blind study was designed to investigate the efficacy of a once-daily (OD) combination of the AT(1) receptor blocker, eprosartan 600 mg, and the thiazide diuretic, hydrochlorothiazide (HCTZ) 12.5 mg, in patients with mild to moderate hypertension (sitting diastolic blood pressure (sitDBP) > or =98 mm Hg and < or =114 mm Hg) not adequately controlled with eprosartan 600 mg OD. A total of 494 patients entered the open-label monotherapy run-in phase, which consisted of eprosartan 600 mg OD for 3 weeks. Patients who responded to monotherapy were not eligible to enter the randomised phase of the study and were withdrawn. The remaining 309 patients were then randomised to either eprosartan 600 mg plus HCTZ 12.5 mg OD or to continue on eprosartan 600 mg OD. In the eprosartan plus HCTZ combination group, both sitDBP and sitting systolic blood pressure (sitSBP) were significantly reduced compared with the eprosartan monotherapy group. In addition, the response rate was higher in the combination group compared with the monotherapy group. There were no significant effects on reduction of sitDBP due to gender, prior use of antihypertensives or baseline severity of hypertension. The tolerability profile for the combination group was similar to that for the monotherapy group. Headache was the most frequent adverse event in both treatment groups. The majority of adverse events were mild to moderate in intensity. In this study of patients who were unresponsive to eprosartan monotherapy for 3 weeks, a combination product of eprosartan 600 mg and HCTZ 12.5 mg was shown to be an effective and well tolerated treatment. (+info)
Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism.
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Hyperuricemia is associated with hypertension and vascular disease, but whether this represents a causal relationship or an epiphenomenon remains unknown. We recently reported a model of mild hyperuricemia in rats that results in increased blood pressure and mild renal fibrosis. In this study, we examined the effect of hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05). Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia or arteriolopathy despite controlling blood pressure. In contrast, the arteriolopathy and hypertension were prevented by both enalapril and losartan. Uric acid also directly stimulated vascular smooth muscle cell proliferation in vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system. (+info)
Diuretic induced hyponatraemia in elderly hypertensive women.
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Diuretics are recommended as first-line antihypertensive treatment in elderly patients. Although attention is usually paid to prevent hypokalaemia with diuretic therapy, risk of hyponatraemia is often ignored. We performed this study to characterise hypertensive patients at increased risk to develop hyponatraemia. We reviewed charts of hypertensive patients hospitalised in Chaim Sheba Medical Center for hyponatraemia from 1990 to 1997. Patients with other causes of hyponatraemia were excluded. The General Practice Maccabi database was used to estimate age and sex distribution of patients prescribed diuretics for hypertension. We identified 180 hypertensive patients (149 F, 31 M; mean age 76.4 +/- 9.2 years) hospitalised because of hyponatraemia. Across all age groups, odds ratio (OR) to develop hyponatraemia was three times higher for women vs men (OR 3.10, 95% confidence interval (CI): 2.07-4.67). One hundred and sixty-two patients (90%) were older than 65 years. Patients of both sexes older than 65 years were 10 times (and if they were older than 75 years 16 times) more likely to develop hyponatraemia than those younger than 65 years (OR 9.87, 95%, CI: 5.93-16.64). Most patients (74.5%) used a thiazide-based diuretic; only 10% used a low dose (<25 mg/day). In 37% of patients diuretics were used for more than 1 year before hyponatraemia developed. Diuretic-induced hyponatraemia may be insidious and appear even after prolonged diuretics use. Elderly women seem to be at particularly high risk. In this population diuretic use should be associated with close monitoring of sodium and potassium levels. (+info)