Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India.

BACKGROUND/OBJECTIVES: Vitamin B(12) (B(12)) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B(12) and folic acid on plasma total homocysteine (tHcy) concentration. SUBJECTS/METHODS: A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. B(12) was given as 2 or 10 microg capsules, with or without 200 microg folic acid, forming six groups (B(0)F(0), B(2)F(0), B(10)F(0), B(0)F(200), B(2)F(200) and B(10)F(200)). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation. RESULTS: From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B(12) and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B(0) vs. B(2) vs. B(10); and F(0) vs. F(200). At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) micromol/l in B(2), and by 7.1 (95% CI: -8.9, -5.4) micromol/l in B(10), compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) micromol/l in B(0). B(2) and B(10) did not differ significantly. In F(200), tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) micromol/l compared to 2.8 (95% CI: -4.3, -1.2) micromol/l in F(0). CONCLUSION: Daily oral supplementation with physiological doses of B(12) is an effective community intervention to reduce tHcy. Folic acid (200 microg per day) showed no additional benefit, neither had any unfavorable effects.

Effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on ADP-induced platelet aggregation.

A randomized, observer-blind, parallel-group study was carried out to compare the effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on platelet aggregation, measured at a time expected to coincide with trough plasma levels of these drugs. 24 patients (age-30 to 60 yrs) with uncomplicated mild to moderate hypertension who completed a placebo run-in phase successfully were recruited in this study. They were randomly allocated to one of the 4 treatments: prazosin GITS 2.5 mg OD (Group 1), atenolol 50 mg OD (Group II), nifedipine SR 20 mg BD (Group III), and enalapril 5 mg OD (Group IV). All the drugs were given for 7 days, and blood samples were collected at 0 hr on day 1 (pre-treatment) and day 8 (post-treatment). Based on the dose (incremental concentrations of ADP)--response (% maximum aggregation) curve obtained, 2.5 microM/L of ADP was used to compare % inhibition of platelet aggregation among the 4 groups. We found that prazosin GITS inhibited % maximum aggregation significantly (p = 0.02) at 2.5 microM/L of ADP. Such inhibitory effect was not seen in any of the other groups. The inhibition produced by prazosin GITS differed significantly from the action of the other 3 drugs (p < 0.05). This antiplatelet effect of prazosin GITS bears more clinical relevance in view of the fact that it was seen at a time which is expected to coincide with the trough plasma levels of prazosin.

Prazosin GITS vs sustained release nifedipine in patients with hypertension and abnormal lipid profile: a randomized, controlled, multicenter study. Madras Hypertension Study Group.

OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and a sustained release (SR) preparation of nifedipine. DESIGN: Randomized, controlled, multicenter study of 26 weeks duration. SETTING: Office practices of 24 physicians in Chennai, Tamil Nadu, India. PATIENTS: Males and females, aged 30 to 70 yrs, with hypertension of JNC V stage 1 or 2 at the end of a 2-week placebo run-in period, and an abnormal lipid profile. Sufficient number of patients recruited so that at least 60 complete the entire study. INTERVENTIONS: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or sustained release nifedipine (Nicardia Retard 10-20 mg twice daily) for upto 6 weeks, continued upto 24 weeks in those showing a pre-defined response (SBP and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual value of DBP < 95 mm Hg). Patients allocated to either of the two interventions by randomization. OUTCOME MEASURES: Percent patients showing pre-defined BP response at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and both; percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those receiving treatment for 24 weeks; mean change in blood glucose and serum lipids at the end of weeks 8, 16, and 24 of treatment; frequency and intensity of adverse events judged probably or definitely related to the drug. RESULTS: 54 patients randomized to prazosin GITS group and 52 to nifedipine SR group. Of these, 39 in prazosin GITS group (M 23, F 16; mean age-50. 6 yr, SEM 1.66) and 36 in nifedipine SR group (M 20, F 16; mean age-52.3 yr, SEM 1.71) completed the study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--100%, nifedipine SR--100%; SBP < 140 mm Hg: prazosin GITS--94.9%, nifedipine SR--91.7%; both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--92.3%, nifedipine SR--91.7%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--76.9%, nifedipine SR--83.3%. The mean fall in the systolic and diastolic blood pressure from the end-of-placebo-phase values to all the other time points was comparable in the 2 groups. Treatment with prazosin GITS did not produce any statistically or clinically significant change in the metabolic parameters at the end of 24 weeks, while with nifedipine SR there was a significant increase in the serum LDL values at 24 weeks (p = 0.009). Adverse events probably or definitely related to the drug: prazosin GITS--1.9%, nifedipine SR--2.1%. CONCLUSION: Both drugs were equally effective and well tolerated. While prazosin GITS was neutral on serum lipids, use of nifedipine SR was associated with a significant increase in serum LDL cholesterol at the end of 24 weeks.

Prazosin GITS vs atenolol in patients with hypertension and normal lipid profile: a randomized, controlled multicenter study. Hyderabad Hypertension Study Group.

OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and atenolol. DESIGN: Randomized, controlled, multicenter study of 26 weeks duration. SETTING: Office practices of 24 physicians in Hyderabad, Andhra Pradesh, India. PATIENTS: Males and females, aged 30 to 70 yrs, with hypertension of JNC V stage 1 or 2 at the end of a 2-week placebo run-in period, and a normal lipid profile. Sufficient number of patients recruited so that at least 60 complete the entire study. INTERVENTIONS: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or atenolol (Tenormin 50-100 mg once daily) for upto 6 weeks, continued upto 24 weeks in those showing a pre-defined response (SBP and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual value of DBP < 95 mm Hg). Patients allocated to either of the two interventions by randomization. OUTCOME MEASURES: Percent patients showing pre-defined BP response at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and both; percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those receiving treatment for 24 weeks; mean change in serum lipids at the end of weeks 8, 16, and 24 of treatment; mean change in laboratory parameters for safety at the end of week 24; frequency and intensity of adverse events judged probably or definitely related to the drug. RESULTS: 62 patients randomized to prazosin GITS group and 60 to atenolol group. Of these, 39 in prazosin GITS group (M 23, F 16; mean age-48.4 yr, SEM 1.60) and 39 in atenolol group (M 24, F 15; mean age-42.9 yr, SEM 1.48) completed the entire study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--92.3%, atenolol--92.3%; SBP < 140 mm Hg: prazosin GITS--89.7% atenolol--94.9% both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--87.2%, atenolol--89.7%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--92.3%, atenolol--100%. The mean fall in the systolic and diastolic blood pressure from the end-of-placebo-phase values to all the other time points was comparable in the 2 groups, except at week 2, when the fall was greater for atenolol (8.8 mm Hg vs 11.4 mm Hg, p = 0.05). Treatment with prazosin GITS resulted in a favourable effect on the serum lipid profile at the end of 24 weeks (p = 0.02 for total cholesterol, p = 0.015 for the ratio of total to HDL cholesterol, p = 0.04 for LDL cholesterol). Atenolol, on the other hand, did not produce any significant change in the metabolic parameters at the end of 24 weeks. Adverse events probably or definitely related to the drug: prazosin GITS--in 10.3% patients, atenolol--in 16.7% patients. CONCLUSION: In the doses used, both prazosin GITS and atenolol had comparable efficacy and tolerability. While atenolol was neutral on serum lipids, prazosin GITS showed a beneficial effect at the end of 24 weeks.

A randomized, controlled, multicenter study to compare prazosin GITS with enalapril in hypertensive patients with diabetes mellitus. Bombay Hypertension Study Group.

OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and enalapril. DESIGN: Randomized, controlled, multicenter study of 26 weeks duration. SETTING: Office practices of 20 physicians in Mumbai, India. PATIENTS: Males and females, aged 30 to 70 yrs, with hypertension of JNC V stage 1 or 2 at the end of a 2-week placebo run-in period, and diabetes mellitus with at least acceptable glycaemic control (FBS < or = 140 mg/dl, 2-hr PMBS < or = 200 mg/dl, and glycosylated hemoglobin < or = 9.5%). Sufficient number of patients recruited so that at least 60 complete the entire study. INTERVENTIONS: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or enalapril (Enam, 5-10 mg once daily) for upto 6 weeks; continued upto 24 weeks in those showing a pre-defined response (SBP and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual value of DBP < 95 mm Hg). Patients allocated to either of the two interventions by randomization. OUTCOME MEASURES: Percent patients showing pre-defined BP response at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and both; percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those receiving treatment for 24 weeks; mean change in serum lipids at the end of weeks 8, 16, and 24 of treatment; mean change in blood sugar and glycosylated hemoglobin at the end of weeks 8, 16, and 24 of treatment; mean change in 12-hr urinary microalbuminuria and laboratory parameters for safety at the end of week 24; frequency and intensity of adverse events judged probably or definitely related to the drug. RESULTS: Forty-Eight patients randomized to prazosin GITS group and 41 to enalapril group. Of these, 31 in prazosin GITS group (M 19, F 12; mean age-53.4 yr, SEM 1.68) and 29 in enalapril group (M17, F 12; mean age-54.7 yr, SEM 1.64) completed the entire study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--71.0%, enalapril--72.4%; SBP < 140 mm Hg: prazosin GITS--54.8%, enalapril--55.2; both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--54.8%, enalapril--44.8%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--77.4%, enalapril--72.4%. The mean fall in the systolic and diastolic blood pressure from the end-of-placebo-phase values to all the other time points was comparable in the two groups. Treatment with prazosin GITS resulted in a favourable effect on serum triglycerides at the end of 8 weeks (p = 0.017) and 16 weeks (p = 0.011), and no detrimental effect or a marginal beneficial effect on total cholesterol, HDL cholesterol, and LDL cholesterol. Enalapril group, on the other hand, showed a significant increase in LDL cholesterol at the end of 24 weeks (p = 0.018), and a marginal increase in total cholesterol, but a beneficial effect on triglycerides at the end of 16 weeks (p = 0.015). Neither drug had any effect on glycosylated hemoglobin and 12-hr urinary microalbuminuria. Treatment with both drugs was associated with an increase in FBS and 2-hr PMBS, but this rise reached statistical significance only in prazosin GITS group. Adverse events probably or definitely related to the drug: prazosin GITS--2 of 44 patients (4.5%), enalapril--6 of 39 patients (15.4%). CONCLUSION: 1. In the doses used, prazosin GITS showed comparable antihypertensive efficacy to enalapril. 2. While enalapril had variable effect, prazosin GITS showed a consistent beneficial effect on some of the serum lipid fractions. 3. The 3-fold difference in the incidence of side effects, although not statistically significant for the available sample size, may be clinically relevant.

Co-existence of hypertension and abnormal lipid profile: a hospital-based retrospective survey.

Indian data on co-existence of coronary risk factors is scanty. This retrospective survey was carried out to estimate the prevalence of abnormal lipid profile and glucose metabolism in hypertensive patients. Records of persons coming for a health check-up were screened to obtain 500 consecutive evaluable records of persons with hypertension or those taking antihypertensive drugs. 57 percent of these subjects had cholesterol > or = 200 mg/dl. An elevated ratio of total to HDL cholesterol (> 4.5) was also present in 47 percent of the subjects. Serum triglycerides were > or = 200 mg/dl in 34 percent of the subjects, and > or = 400 mg/dl in 5 percent. These lipid abnormalities were more prevalent in males than females (p < 0.05). 20 percent of all the subjects were either on antidiabetic drugs or had fasting blood sugar more than 120 mg/dl.

Prevalence of lipid and glycaemic abnormalities in hypertensive patients: a retrospective survey.

A number of coronary heart disease (CHD) risk factors such as dyslipidaemia and diabetes are known to coexist along with hypertension, itself a major CHD risk factor. Indian data on the coexistence of these risk factors is scanty. Epidemiologic studies in India have focused more on the prevalence of CHD in various communities or the correlation of various risk factors with CHD. However, we could not find any large-scale study showing the prevalence of lipid and glycaemic abnormalities in hypertensive patients. This retrospective survey was therefore carried out to estimate the prevalence of metabolic (lipid and glycaemic) abnormalities in hypertensive subjects. The records of persons coming for a health check-up at the Apollo hospitals were screened to obtain 501 consecutive evaluable records of patients who had hypertension or were taking antihypertensive drugs. We found that in 57 percent of these, the levels of total cholesterol were > or = 200 mg/dl and in 37 percent, LDL cholesterol was > or = 130 mg/dl. An elevated ratio of total to HDL cholesterol (> 4.5) was present in 11 percent of patients. Serum triglycerides were > or = 200 mg/dl in 30 percent, and > or = 400 mg/dl in 6 percent. Thirty-six percent of all the hypertensives were either on antidiabetic drugs or had fasting blood sugar values of more than 120 mg/dl. Our findings are thus in agreement with those for the Western population.

Prazosin in chronic congestive heart failure due to ischemic heart disease.

Oral prazosin hydrochloride (2-20 mg/day) was administered to 38 patients with chronic congestive heart failure due to ischemic heart disease for 6-18 months. Half (19) of the patients were hypertensive and half (19) nonhypertensive. All were receiving furosemide (80 mg/day, orally) and 19 were receiving digoxin (0.25-0.5 mg/day, orally) in addition to prazosin. Clinical radiological, mechanocardiographic, echocardiographic, and biochemical observations were made initially, at peak response, and at the end of 6 months. Prazosin improved left ventricular function indexes at rest, relieved symptoms and signs of congestion, and remained effective for 6-18 months with little or no increase in dose. There was no reflex tachycardia, tension-time indexes fell in all patients, angina was relieved in 8 patients who complained of it, and dyskinesia of left ventricular wall was corrected in 8 of 13 patients. The New York Heart Association functional class improved in all patients, but to a greater extent in hypertensive patients and in those not receiving concomitant digoxin. Mild, transient side effects occurred in 6 patients.

Statistics for clinicians. 5. Interval data (I).

Interval data may be discrete or continuous. They are usually summarized by the average (arithmetic mean). Sometimes, for example when the possible values in a series change by a constant multiple, we need to use the geometric mean. To obtain the overall or mean percentage of a series of percentage values, we need to calculate their weighted mean. The variability of observations in a sample is measured by the standard deviation, and the variability of sample means is measured by the standard error of mean. Confidence interval is a range which contains the population mean with a known probability. It is obtained by deducting from the sample mean, and adding to it, "t" times the SEM, the value of "t" depending on the desired confidence level (1-P) and the sample size (N). The significance of difference between the mean of two sets of unpaired interval data (MA-MB) is tested by Student's t-test. If the data are paired, the significance of the mean difference (MD) is tested by paired t-test. Ordinal data, ie, grades and ranks, may be analyzed by means of the t-test which is more sensitive and allows more refined analyses if needed.

Statistics for clinicians. 3. Nominal data (II)

When the percentage occurrence of an event in a series of groups shows a linear trend, the standard chi-square test may not reveal its significance. The data should then be analyzed by z-test for a linear trend. When the results of several similar experiments show a trend in favor of one group, but the differences in individual studies are not significant, the data from all studies can be analyzed together by the z-test for significance of the trend. In some studies, patients need to be followed up for long periods for the occurrence of an event. Here, we are interested not only in the frequency of the event, but also how soon it occurs or how long it is delayed. For this purpose the data should be analyzed by the life table method (also known as the logrank method or the Mantel-Haenszel method). Diagnostic tests are usually evaluated by their sensitivity and specificity. However, what is also important for a clinician is their predictive value, which depends on the prevalence of the condition.

Statistics for clinicians. 2. Nominal data (I).

Nominal data consist of items assigned to well defined classes. They are presented as a proportion or percentage of the total. From a sample percentage we can estimate the population percentage with a desired degree of confidence, using standard error of the percentage as a measure of chance variation. We can compare the difference in percentage between two groups by means of the z-test or the chi-square test. If the number of observations is less than 40, Fisher's test is preferable to the chi-square test. When chi-square test is done on 2x2 tables, Yates' correction is recommended. For tables larger than a 2x2, Yates' correction is not used. When testing paired data for significance of difference, we need to use McNemar's modification of Chi-square test. Chi-square test is useful not only to test the significance of differences but also to test the significance of an association between attributes.