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Issues raised recently concerning the safety of calcium channel blockers (CCBs) prompted an analysis of the occurrence of cardiovascular events and death in the Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and nifedipine in the gastrointestinal therapeutic system (GITS) formulation (Procardia XL). Prospectively defined analyses of data from comparative and noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome measures included cardiovascular and noncardiovascular deaths, and adverse cardiovascular events including new/worsened angina, myocardial infarction (MI), serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all amlodipine-treated patients (n = 32,920), the incidence rates for all-cause death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of exposure, respectively. Among those in comparative trials alone (n = 4,126), the all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of other non-CCB agents and significantly less than that of other CCBs (23.8/1,000 patient-years, p = 0.015), although the difference in rates represents only 2 deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all-cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and other cardiac events were low in these hypertension trials, and did not differ among treatment groups in either the amlodipine or nifedipine GITS comparative analyses. In the clinical trial databases analyzed, there is no signal suggesting excessive risk of death or cardiovascular events for hypertensive patients treated with amlodipine or nifedipine GITS. [ABSTRACT FROM AUTHOR]

This study assesses and evaluates left ventricular (LV) contractile function after treatment of hypertension, with an emphasis on LV midwall mechanics. Although prior studies have assessed cardiac function after hypertension treatment, none has performed an analysis of LV midwall mechanics. The Veterans Affairs Study of monotherapy in hypertension was a study large enough to permit analysis of midwall mechanics across a wide spectrum of mass changes accompanying hypertension treatment. LV chamber function was assessed by computing fractional shortening at the endocardial surface; LV midwall shortening was used to define myocardial function. Both shortening indexes were related to end-systolic circumferential stress in the entire population by partitioning values of mass and relative wall thickness changes. Two hundred sixty-eight patients were studied at baseline and again after a 1- or 2-year period. In the entire group, there was no significant change in circumferential shortening either at the endocardium (38 +/- 8% at baseline vs 37 +/- 7% at follow up, p = 0.29) or in shortening at the midwall (20 +/- 3% vs 20 +/- 3%, p = 0.53). However, 83 patients had a reduction in relative wall thickness and an increase in midwall shortening. The change in midwall shortening was significantly related to changes in relative wall thickness (r = -0.53, p = 0.0001). Thus, reductions in LV mass associated with antihypertensive therapy are generally not accompanied by a decrement in LV chamber or myocardial function. Improvement in midwall shortening is more closely related to normalization of LV geometry than to reduction in LV mass.

An abnormal plasma lipid and lipoprotein profile is an independent and strong predictor of mortality and morbidity from coronary artery disease (CAD). We report on plasma lipid and lipoprotein profiles with respect to race, age, obesity, blood pressure (BP), smoking, and drinking history in 1,292 male veterans with a diastolic BP of 95 to 109 mm Hg while off antihypertensive medications. Blacks had 24% (p <0.001) lower triglycerides than whites. In contrast, the following parameters were higher in blacks than in whites by the indicated percentages: high-density lipoprotein (HDL) cholesterol, 16% (p <0.001); HDL2 cholesterol, 36% (p <0.001); apolipoprotein (Apo) A1, 8% (p <0.001); HDL/low-density lipoprotein (LDL), 18% (p = 0.018); HDL2/LDL, 36% (p = 0.031); HDL2/HDL3, 21% (p <0.001); and Apo A1/Apo B, 15% (p <0.001). Triglycerides were unchanged up to age 60, but were lower by 24% (p <0.001) in those aged > or = 70. Apo A1 levels were higher (p <0.001), whereas LDL cholesterol was lower (p <0.008) in moderate alcohol consumers versus abstainers. Triglycerides were higher (p <0.001), whereas HDL, HDL2 cholesterol, and Apo A1 were lower (p <0.001) with increasing obesity. Moderate alcohol consumption had a strong favorable effect on HDL, HDL2, and HDL3 cholesterol among subjects of normal weight, but this effect was diminished in obese subjects. Total and LDL cholesterol were higher by 6.4% (p = 0.001) and 9.4% (p <0.003), respectively, whereas HDL cholesterol remained unchanged in those with diastolic BP of 105 to 109 mm Hg versus those with diastolic BP of 95 to 99 mm Hg. We conclude that hypertensive black men have lipid and lipoprotein profiles indicative of less CAD risk than white men. Chronic moderate alcohol consumption correlates with a favorable plasma lipid and lipoprotein profile in normal, but not obese, men. Obesity is associated with an adverse plasma lipid and lipoprotein profile. Thus, race, alcohol intake, and obesity may be important modifiers of CAD in untreated hypertensive men.

Angiotensin-converting enzyme (ACE) inhibitors are useful first-line drugs in the therapy of mild and moderate hypertension. Adverse reactions to this drug class are rarely serious. Hypotension, cough, rash, and taste disturbance are uncommon; reduced glomerular filtration and hyperkalemia occur infrequently; angioedema is rare and neutropenia is extremely rare. Quinapril is a new ACE inhibitor that is converted to biologically active quinaprilat in the liver. This ACE inhibitor has a rapid onset of action and inhibits local tissue converting enzyme systems in kidney, heart, and brain, as well as in the circulating renin-angiotensin system. Clinically significant adverse effects of quinapril occur at low rates. In 1,771 patients receiving quinapril, the reported incidence of the first occurrence of orthostatic hypotension was comparable to that seen in patients receiving placebo. In other studies, headache was reported by up to 4.7% of patients receiving quinapril, which is comparable to reported incidences of headache in patients receiving other ACE inhibitors. Other adverse events reported at rates greater than 1% include cough with associated rhinitis and bronchitis, dizziness, and somnolence. Such adverse events have only rarely led to the withdrawal of patients from clinical studies of quinapril.

Left ventricular (LV) diastolic filling pattern of obese subjects with eccentric LV hypertrophy was studied. Findings were compared with those of normal control subjects and hypertensive patients with concentric LV hypertrophy. M-mode, 2-dimensional and Doppler echocardiograms were recorded in 11 obese (body mass index greater than 30 kg/m2) normotensive patients with eccentric LV hypertrophy, 10 normal control subjects, and 18 nonobese, hypertensive patients with concentric LV hypertrophy whose antihypertensive medications were discontinued 2 weeks before study. LV hypertrophy was defined as LV mass/height greater than 143 g/m. Hypertrophy in the obese patients was eccentric: Their LV internal dimension (61 +/- 3 mm) was greater than that of hypertensive patients (55 +/- 5 mm, p less than 0.001) and normal control subjects (55 +/- 2 mm, p less than 0.01); their septal (10.7 +/- 0.7 mm) and posterior (10.9 +/- 0.6 mm) wall thicknesses were smaller than those of the hypertensive patients (12.2 +/- 1.7 mm, p less than 0.05 and 11.7 +/- 1.2 mm, respectively, difference not significant). Pulsed-wave Doppler echocardiographic filling indexes were used to evaluate LV diastolic filling. Obese patients had a higher peak velocity of atrial filling (69 +/- 14 vs 54 +/- 15 cm/s, p less than 0.05), lower early/atrial filling velocity ratio (1.0 +/- 0.26 vs 1.32 +/- 0.21, p less than 0.05), prolonged deceleration half-time (108 +/- 9 vs 86 +/- 15 ms, p less than 0.01) and lower peak filling rate corrected to stroke volume (4.08 +/- 0.68 vs 4.96 +/- 0.88 stroke volume/s, p less than 0.05) than normal control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Right (RV) and left ventricular (LV) diastolic function was evaluated in 50 patients with mild, uncomplicated essential hypertension using pulsed-wave Doppler echocardiography. Patients with pulmonary, valvular or coronary artery disease were excluded and antihypertensive drugs were discontinued for the 2 weeks preceding the study. Ten normotensive patients without heart disease acted as control subjects. In the hypertensive patients, RV peak velocity of atrial filling was higher (42 +/- 10 vs 31 +/- 7 cm/s, p less than 0.01) and deceleration half-time was prolonged (96 +/- 20 vs 83 +/- 10 ms, difference not significant); ratio of early/atrial filling velocity (1.1 +/- 0.3 vs 1.7 +/- 0.4, p less than 0.001) and peak filling rate corrected to stroke volume (3.6 +/- 0.7 vs 5.3 +/- 0.9 SV/s, p less than 0.001) were lower. LV filling parameters showed similar changes. RV filling parameters did not correlate with age, LV mass or septal thickness but correlated weakly with LV radius/thickness ratio. There was good correlation between RV and the following corresponding LV filling parameters: peak filling rate, r = 0.68, p less than 0.001; ratio of early/atrial filling, r = 0.88, p less than 0.0001; and deceleration half-time, r = 0.62, p less than 0.001. Data indicate that RV diastolic function is abnormal in essential hypertension and these abnormalities are closely related to those of LV diastolic function.

Dilevalol combines vasodilation due to selective beta 2 agonism and nonselective beta antagonism. We studied 311 patients randomized to dilevalol and 138 to metoprolol in a multicenter trial. After a 4-week placebo washout, dilevalol was titrated from 200 to 1,600 mg once daily and metoprolol from 100 to 400 mg to a goal supine diastolic blood pressure less than 90 and greater than or equal to 10 mm Hg decrease from baseline. Responders were followed for 1 year. The average age of patients was 51 years; 72% were men and 54% were white. Both drugs reduced blood pressure effectively to a similar level. Fewer patients discontinued dilevalol than did those taking metoprolol (9 vs 16%; p less than 0.03). More metoprolol-treated patients withdrew because of depression (6 vs less than 1%; p = 0.03) and impotence (5 vs less than 1%; p = 0.03). Lipoprotein levels before and after treatment were measured in 99 patients treated for 53.5 weeks with dilevalol (mean dose 438 mg). Dilevalol increased high-density lipoprotein (HDL) cholesterol by 2.5 mg/dl to 47.2 (p = 0.05), reduced low-density lipoprotein (LDL) cholesterol by 2.5 mg/dl, increased HDL/LDL by 0.03, and decreased total cholesterol/HDL cholesterol by 0.18. Triglycerides increased by 21 mg/dl (p = 0.06). In patients with an initial HDL cholesterol less than 35 mg/dl, dilevalol increased it by 9 mg/dl. In patients treated with metoprolol, the only significant change (p = 0.02) was a 41.9-mg/dl increase in triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Guanfacine, an alpha-adrenoceptor agonist, may exhibit distinct dose-related curves for efficacy and adverse effects in the step-2 therapy of essential hypertension. To determine the lowest clinically effective safe dose, 462 newly or previously diagnosed subjects were admitted to a 5-week prerandomization phase at 8 centers. Patients were weaned from any current antihypertensive drugs and placed on 25-mg chlorthalidone, daily, in the morning. At the end of the 5-week weaning period, 362 patients with seated diastolic blood pressures (BPs) between 95 and 114 mm Hg qualified for the 12-week postrandomization phase. Subjects were randomized to receive either an indistinguishable placebo or 0.5, 1, 2 or 3 mg of guanfacine. Chlorthalidone was changed to bedtime administration and taken with the study medications. Guanfacine was started at the lowest dose in all subjects and increased (if scheduled, according to the randomization code) to the next higher dose at biweekly intervals. Of the 362 randomized patients, 278 completed the study. The 1-mg guanfacine dosage produced a 14/13 mm Hg decrease in BP (p less than 0.0125 compared with placebo). Doses of guanfacine at 2 and 3 mg/day were not more effective than the 1 mg/day dose; 0.5 mg/day was not better than placebo. There was an increase in the frequency of side effects possibly or probably associated with 2 and 3 mg/day guanfacine. Only 3.2% of the patients in the 1 mg/day group dropped out of the study because of side effects. We conclude that when added to a diuretic, 1 mg/day guanfacine at bedtime is the lowest safe and therapeutically effective dose.

The blood pressure-lowering effects of a calcium-entry blocker, diltiazem (240 or 360 mg/day), and a thiazide diuretic, hydrochlorothiazide (50 or 100 mg/day), were studied in 20 black hypertensive patients. Supine blood pressure decreases of -34/-18 mm Hg for diltiazem and -29/-21 mm Hg for hydrochlorothiazide were noted after 14 weeks of therapy. Differences between drugs were not significant. Blood pressures were normalized in all 4 of the monotherapy nonresponders when the 2 drugs were combined. Significant adverse effects were not noted. These data suggest that diltiazem is an effective antihypertensive agent in black patients. As monotherapy, its blood pressure-lowering effect is equivalent to hydrochlorothiazide.