Calcium entry blockers for systemic hypertension

Calcium entry blockers appear to be effective antihypertensive agents in both young and older patients. Studies comparing diltiazem and placebo, diltiazem and propranolol, and diltiazem and hydrochlorothiazide indicate that this calcium entry blocker is more effective than placebo, equally effective as the beta-adrenergic inhibitors at least in short-term studies, but not as effective in lowering systolic blood pressure (BP) when compared with hydrochlorothiazide (diastolic BP -11.5 mm Hg with diltiazem vs -12.2 mm Hg with hydrochlorothiazide; systolic BP -12.2 mm Hg with diltiazem vs -20.0 mm Hg with hydrochlorothiazide). Combination therapy with diltiazem and hydrochlorothiazide proved effective in a high percentage of mono-therapy nonresponders. The most common adverse reactions to diltiazem included headaches, dizziness and edema. The exact place of calcium entry blockers in therapy as initial or step-2 therapy with a diuretic in hypertension must be determined by additional long-term experience in large numbers of patients.     

Regular formulation and sustained-release verapamil therapy in normotension and in mild to moderate hypertension

Calcium entry blocker drugs have hypotensive effects that are mediated by both cardiac and noncardiac actions. Dihydropyridine calcium blockers, such as nifedipine and nicardipine, are potent vascular smooth muscle relaxants that lower blood pressure by decreasing peripheral arteriolar resistance. Reflex tachycardia, however, may blunt the magnitude of their hypotensive effect, especially in patients with increased baroreflex sensitivity. Nondihydropyridine calcium blocker drugs, such as verapamil and diltiazem, exert their hypotensive action by both cardiac and peripheral circulatory mechanisms. These drugs also act as arteriolar vasodilators. In addition, they slow the heart rate by decreasing the automaticity of sinoatrial pacemaker cells in the heart. The combined negative chronotropic and vasodilatory actions are especially useful in hypertensive patients with baroreflex sensitivity who are prone to fast heart rates, and in hypertensive patients with associated coronary artery disease. Coronary heart disease patients with or without coexisting hypertension usually show reduction in systolic blood pressure (SBP) and heart rate (HR) both at rest and during submaximal exercise on the treadmill or bicycle. A reduced double product (SBP X HR) with submaximal exertion results in a decrease in cardiac work and correlates with enhanced exercise capacity and delay in onset of angina during exercise testing. In some patients with both hypertensive and coronary heart diseases and ventricular dysrhythmias emerging during exercise, verapamil may confer antiarrhythmic as well as antihypertensive and antianginal benefits. At present, calcium blocker drugs, which have an elimination half-life of 3 to 6 hours, must be given 3 times a day for effective antihypertensive control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved left ventricular filling accompanies reduced left ventricular mass during therapy of essential hypertension

Abnormal left ventricular diastolic performance, an early manifestation of hypertension in the heart, may precede the development of left ventricular hypertrophy. To assess effects of antihypertensive therapy on the heart, left ventricular mass (determined by echocardiography) and rapid left ventricular filling rate (determined by radionuclide ventriculography) were compared before and after 6 months of treatment of 16 patients. Nitrendipine (a dihydropyridine calcium channel blocker) was given alone or in combination with either propranolol or hydrochlorothiazide, or both, and significantly reduced blood pressure (156/103 +/- 12/7 to 137/89 +/- 10/6 mm Hg). In 6 of the 16 patients, left ventricular mass decreased by more than 10% (270 +/- 95 to 193 +/- 47 g, p less than 0.01); in the same patients, left ventricular filling rate increased (2.03 +/- 0.35 to 2.30 +/- 0.45 end-diastolic counts/s [EDC/s], p less than 0.01). In the one patient whose left ventricular mass increased (137 to 195 g), left ventricular filling rate decreased from 2.01 to 1.78 EDC/s. In the remaining nine patients who had no change in left ventricular mass, there was no significant changes in left ventricular filling. The changes in ventricular mass and filling could not be related to the extent of change in blood pressure or heart rate. These data suggest that regression of left ventricular mass during antihypertensive therapy with nitrendipine is accompanied by improved diastolic function.     

Hydrochlorothiazide is not additive to verapamil in treating essential hypertension

Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170 +/- 17/109 +/- 6 mm Hg pretreatment to 150 +/- 25/95 +/- 8 mm Hg with verapamil; 170 +/- 5/109 +/- 2 mm Hg pretreatment to 164 +/- 25/103 +/- 10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150 +/- 25/95 +/- 8 mm Hg vs 150 +/- 20/95 +/- 6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2 +/- 0.25 mmol/L to 3.7 +/- 0.35 mmol/L) and stimulated plasma renin activity (1.5 +/- 1.3 ng/mL/h) pretreatment to 3.3 +/- 2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 +/- 1.3 ng/mL/h pretreatment to 2.7 +/- 2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted.     

Thiazide therapy is not a cause of arrhythmia in patients with systemic hypertension

Forty-four patients with uncomplicated systemic hypertension underwent 48-hour electrocardiographic monitoring before and after four weeks of treatment with hydrochlorothiazide, 100 mg daily. Plasma potassium concentration decreased from 4.07 +/- 0.26 mmol/L (4.07 +/- 0.26 mEq/L) to 3.36 +/- 0.44 mmol/L (3.36 +/- 0.44 mEq/L). The average number of premature ventricular contractions, couplets, or ventricular tachycardia episodes did not change significantly. Twenty patients had more than minimal ventricular ectopy (class 2 to 5) before and 17 after diuretic therapy. Further analysis revealed that following diuretic therapy, neither patients with plasma potassium levels of 3.4 mmol/L or less (less than or equal to 3.4 mEq/L) nor patients with left ventricular hypertrophy had increased ectopy as compared with baseline. At baseline, patients with left ventricular hypertrophy had more arrhythmias than patients without. We conclude that the results of this study provide no evidence that diuretic therapy or diuretic-induced hypokalemia results in increased ventricular ectopy, and that patients with left ventricular hypertrophy may have more ventricular ectopy than patients without, but these arrhythmias are not adversely effected by diuretic therapy.     

The prevalence of cardiac ectopy in elderly patients with echocardiographically normal hearts is not increased by significant coronary artery disease

ISSUE: A higher frequency of abnormal heart rhythms has previously been shown in elderly subjects with overtly normal hearts as demonstrated by noninvasive testing. However, no prior study on elderly patients with echocardiographically structurally normal hearts has distinguished cardiac dysrhythmia incidence based on the presence or absence of angiographically documented coronary artery disease (CAD). METHODS: We performed 24-hour ambulatory monitoring on patients with no coronary stenosis of greater than 30% and normal left ventricular (LV) systolic function by angiography. This group was then compared with a group of elderly patients with normal LV systolic function and at least one major coronary artery stenosis of 70% or greater. All patients had echocardiographically normal LV wall thickness and systolic function and no significant valvular disease. RESULTS: The experimental group was composed of 15 patients with CAD aged 71 +/- 6 years. The control group without significant CAD was composed of 20 patients aged 73 +/- 4 years (P = not significant [NS]). There was no difference with respect to prevalence of hypertension, use of calcium-channel blockers, and history of smoking. There was no difference between the groups with regard to the number of premature atrial contractions (467 +/- 759 [experimental] vs 672 +/- 1789 [control]; P = NS); premature ventricular contractions (359 +/- 599 [experimental] vs 290 +/- 858 [control]; P = NS); and prevalence of ventricular couplets, ventricular tachycardia, paroxysmal atrial fibrillation, and supraventricular tachycardia (all P = NS). CONCLUSIONS: These findings indicate that the prevalence of cardiac dysrhythmias in elderly patients with echocardiographically normal hearts is not influenced by the presence of angiographically significant CAD.     

Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy

Recent studies have suggested that hypertensive patients with ECG evidence of left ventricular hypertrophy (LVH) may have increased risk of sudden death when treated with diuretics. In the present study echocardiography was used as a more sensitive index for the presence of LVH. Thirty-one patients with uncomplicated hypertension underwent 48-hour ambulatory ECG monitoring both before any treatment and after 4 weeks of hydrochlorothiazide, (HCTZ), 100 mg daily. In 18 patients with left ventricular posterior wall thickness (LVPWT) greater than or equal to 13 mm (average = 14.4 +/- 0.2 mm) on echocardiogram, plasma potassium decreased from 4.1 +/- 0.3 to 3.3 +/- 0.4 mEq/L with HCTZ (p less than 0.01). Premature ventricular contractions (PVCs) averaged 5.7 +/- 9.9/hr at baseline and 7.1 +/- 16.6/hr following HCTZ (p = NS). The total number of couplets was 29 before and 13 after HCTZ, while four brief runs of ventricular tachycardia occurred only before treatment. In the remaining 13 patients with LVPWT less than or equal to 12 mm (average = 11.2 +/- 0.1 mm), plasma potassium decreased from 4.1 +/- 0.3 to 3.4 +/- 0.5 mEq/L with HCTZ (p less than 0.01). The average number of PVCs was 4.3 +/- 8.0/hr after HCTZ (p = NS). One couplet and one 3-beat run of ventricular tachycardia occurred before and one 3-beat run of ventricular tachycardia after HCTZ. Although more complex arrhythmias were noted in the LVH group, the differences were not statistically significant. These results indicate that thiazide therapy does not increase ventricular arrhythmias either in patients with or without LVH.     

Risk Reduction Following Regression of Cardiac Hypertrophy

Cardiac hypertrophy in essential hypertension is documented to be an independent risk factor for congestive heart failure, coronary heart disease and cardiac sudden death. Reduction of left ventricular hypertrophy therefore emerged as a new challenge of antihypertensive treatment. Sympatholytic agents, calcium entry blockers, and angiotensin converting enzyme inhibitors have been found to reduce left ventricular hypertrophy, whereas vasodilators (and most likely also diuretics) are unable to reduce left ventricular mass despite good control of arterial hypertension. Several studies indicated that reduction of left ventricular hypertrophy is not detrimental to cardiac pump function: systolic and diastolic function were found to be maintained at rest and during exposure to increased pressure load. In hypertensive patients with left ventricular hypertrophy ventricular arrythmias have been reported to be increased and to be the pathophysiological link for the increased risk of cardiac sudden death. Reduction of cardiac hypertrophy was found to be accompanied by a reduction of prevalence and severity of ventricular arrhythmias if treated with betablockers, calcium entry blockers or converting enzyme inhibitors. Whether reduction of cardiac hypertrophy indeed decreases the cardiovascular risk attributed to left ventricular hypertrophy is unknown at present, although clinical studies support such a viewpoint.     

Angiotensin receptor blocker added to previous antihypertensive agents on arteries of diabetic hypertensive patients

Lowering elevated blood pressure (BP) in diabetic hypertensive individuals decreases cardiovascular events. We questioned whether remodeling of resistance arteries from hypertensive diabetic patients would improve after 1 year of tight BP control with addition of either the angiotensin receptor blocker (ARB) valsartan or the beta-blocker (BB) atenolol to previous therapy, which included angiotensin-converting enzyme inhibitors (ACEIs) and/or calcium channel blockers. Twenty-eight hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving ARBs or BBs) were randomly assigned to double-blind treatment for 1 year with valsartan (80 to 160 mg) or atenolol (50 to 100 mg) daily, added to previous therapy. Resistance arteries dissected from gluteal subcutaneous tissues were assessed on a pressurized myograph. After 1 year of treatment, systolic and diastolic BP and glycemia were equally well controlled in the valsartan and atenolol groups. Endothelium-dependent and independent relaxation did not change in the treated groups. After 1 year of treatment, resistance artery media:lumen ratio decreased in the valsartan group (7.9+/-0.5% after versus 9.8+/-0.6% before; P < 0.05) but not in the atenolol-treated group (9.9+/-0.9% versus 10.6+/-1%; P value not significant). Artery walls from atenolol-treated patients became stiffer, with no change in the valsartan-treated patients. In conclusion, similar intensive BP control for 1 year with valsartan was associated with improved structure of resistance arteries in diabetic hypertensive patients, whereas vessels from atenolol-treated patients exhibited unchanged remodeling and a stiffer wall. The addition of ARBs but not BBs to antihypertensive medications that may include angiotensin-converting enzyme inhibitors and/or calcium channel blockers results in an improvement in resistance artery remodeling in diabetic hypertensive patients.     

Comparison of nitrendipine and hydrochlorothiazide for systemic hypertension

Left ventricular (LV) hypertrophy with associated LV systolic and diastolic dysfunction is frequently found in patients with systemic hypertension, and is multifactorial in origin. Although a reduction in blood pressure (BP) often results in regression of hypertrophy, the pharmacologic profiles of the antihypertensive agents used may determine the probability of such regression despite similar levels of BP reduction. Thiazide diuretic drugs may actually result in increased LV hypertrophy; calcium channel antagonists may cause regression or no change. The effects of treatment with nitrendipine (20 mg/day) or hydrochlorothiazide (50 mg/day) were compared in an 8-week, double-blind study of 18 hypertensive subjects aged 50 years or older. BP was significantly reduced (p less than 0.05) by both nitrendipine (from 161 +/- 29/102 +/- 4 to 145 +/- 24/92 +/- 7 mm Hg; mean +/- standard deviation) and hydrochlorothiazide (from 162 +/- 15/105 +/- 6 to 143 +/- 20/95 +/- 7 mm Hg). Plasma norepinephrine increased in the nitrendipine group, from 202 +/- 110 to 332 +/- 220 pg/ml at 8 weeks of therapy and in the hydrochlorothiazide group, from 147 +/- 130 to 313 +/- 277. Plasma renin activity changed from 3.2 +/- 2.4 to 3.5 +/- 2.1 during nitrendipine treatment, but from 2.1 +/- 2.1 to 10.5 +/- 10.8 ng angiotensin l/ml/90 min (p less than 0.05) during treatment with hydrochlorothiazide. Left ventricular mass index did not change significantly with either therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular function and collagen content after regression of hypertensive hypertrophy

To determine whether regression of hypertensive hypertrophy through blood pressure control also involves left ventricular collagen and consecutive alterations in left ventricular diastolic and systolic function, antihypertensive treatment with the calcium channel blocker nifedipine (30 mg/kg.day) was employed in 20-week-old spontaneously hypertensive rats (n = 15) for a period of 20 weeks. Age-matched (40 weeks old) untreated (n = 13) and 20-week-old spontaneously hypertensive rats representing the state before therapy (n = 14) were used for comparison. Myocardial stiffness was described by the tangent modulus Km of the elastic stiffness-stress relation. Left ventricular collagen was determined by means of hydroxyproline (OH-proline) concentration. Myocardial working capacity of the left ventricle was measured as the peak developed systolic pressure per weight unit muscle mass and systolic peak pump function as the maximum achievable cardiac output under volume loading. After the 20-week course of nifedipine treatment, systolic aortic pressure dropped from 187 +/- 11 to 144 +/- 6 mm Hg (p less than 0.001). Regression of hypertrophy was shown by a left ventricular muscle/body weight ratio of 2.13 +/- 0.18 mg/g (p less than 0.01) in the 40-week-old nifedipine-treated hypertensive rats, whereas the ratios of the 20-week-old and 40-week-old untreated spontaneously hypertensive rats were 2.3 +/- 0.30 and 2.34 +/- 0.18 mg/g, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Essential hypertension of Caribbean Hispanics: sodium,renin, and response to therapy

Little is known about essential hypertension in Hispanic Americans, despite the fact that they are the fastest-growing minority in the United States and have a disproportionate degree of hypertensive target organ damage. The authors studied 89 Caribbean Hispanic hypertensive patients who participated in six double-blind, randomized trials of antihypertensive agents. Demographics, laboratory data, sodium excretion, plasma renin activity, and atrial natriuretic peptide were obtained after 3-4 weeks on placebo. Blood pressure responses to angiotensin-converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers, hydrochlorothiazide (HCTZ), and fixed combinations of ACE inhibitors and HCTZ, were compared to the placebo values after 8-12 weeks of treatment. Patients had a multiple risk factor profile (obesity and diabetes) and a wide spectrum of blood pressure elevation, left ventricular hypertrophy, and hypertensive renal damage. Urine sodium excretion rates indicated inability to comply with salt restriction in 65% of patients. Plasma renin activity was lower than that of Hispanic normotensive controls, and 62% of patients had low-renin essential hypertension by renin profiling to sodium excretion. On analysis of variance, blood pressure reductions by calcium channel blockers, HCTZ, and ACE inhibitor/HCTZ combinations were significantly greater than that with placebo, while those of ACE inhibitors and beta blockers as monotherapy were not. The authors conclude that essential hypertension of Caribbean Hispanics is associated with multiple risk factors and is largely of the low-renin type. Responses to therapy are consistent with those observed in other populations with the low-renin phenotype and suggest salt-sensitivity of blood pressure in this population. Confirmation of the latter has implications for prevention and treatment of essential hypertension in Hispanics.     

Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations

Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. CONCLUSIONS: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.     

Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans

Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.     

Effect of blood pressure reduction on abnormal left atrial appendage function in untreated systemic hypertensive patients with sinus rhythm

To investigate whether reduction in blood pressure has a beneficial effect on left atrial appendage (LAA) function, the authors evaluated 24 untreated systemic hypertensive patients with normal left ventricular systolic function in sinus rhythm at baseline and at 3 months after initiation of antihypertensive therapy. They performed transthoracic and transesophageal echocardiographic examinations in hypertensive patients before and after treatment of hypertension. Three of the 24 patients had blood pressure that failed to respond to the regimen of antihypertensive therapy and were removed from the analysis. Of the remaining 21 patients, mean systolic and diastolic blood pressures at baseline were 170 +/- 18 and 104 +/- 6 mm Hg, respectively, and fell significantly at 3 months to 141 +/- 10 and 90 +/- 5 mm Hg, respectively, (p<0.001) after initiation of antihypertensive therapy. There was no significant change in heart rate with treatment (baseline 81 +/- 8 and at 3 months 84 +/- 9 beats/min). There was no significant change in left ventricular end-diastolic diameter, left ventricular ejection fraction, left ventricular wall thickness, or left atrial diameter from baseline (49 +/- 4 mm, 58 +/- 5%, 12 +/- 1 mm, and 41 +/- 4 mm, respectively) at 3 months (48 +/- 5 mm, 59 +/- 4%, 12 +/- 1 mm, and 40 +/- 3 mm). The treatment caused a significant reduction in maximal LAA areas (6.3 +/- 1.3 cm2 at baseline, 4.6 +/- 0.7 cm2 at 3 months, p<0.001), with a concomitant increase in LAA emptying velocity (44 +/- 7 cm/sec at baseline, 60 +/- 9 cm/sec at 3 months, p<0.001). In conclusion, these findings suggest that reduction in blood pressure with antihypertensive therapy could improve LAA function in hypertensive patients with normal left ventricular systolic function in sinus rhythm.     

Nifedipine in severely hypertensive patients with congestive heart failure and preserved ventricular systolic function

Nifedipine was used successfully in nine patients with refractory hypertension and left ventricular hypertrophy who had symptoms of congestive heart failure despite preserved left ventricular systolic function. The administration of 10 or 20 mg of nifedipine resulted in an acute decline in BP, from 211 +/- 8/105 +/- 6 mm Hg to 153 +/- 9/78 +/- 5 mm Hg. Six patients received nifedipine and one patient received long-term verapamil therapy (mean follow-up, 16 +/- 4 weeks). In addition to sustained BP control, signs and symptoms of congestive heart failure were greatly improved in all patients treated long term with calcium channel antagonists. No adverse reactions were reported, but a short duration of action limited their usefulness in some patients. Nifedipine seems to be particularly beneficial in this subgroup of severe hypertensive patients with heart failure presumably due to diastolic stiffness of the left ventricle.     

Effect of antihypertensive monotherapy and combination therapy on arterial distensibility and left ventricular mass

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs) increase arterial compliance and decrease left ventricular mass in hypertensive patients. This study examined whether combined therapy has greater arterial and cardiac effects than doubled doses of the individual drugs. METHODS: This prospective, randomized, open-label study enrolled 106 patients aged >/=18 years with mild-to-moderate hypertension. Patients were randomized to 5 mg of amlodipine or 20 mg of benazepril for 2 weeks; then, depending on randomization assignment, they were force-titrated to 10 mg of amlodipine or 40 mg of benazepril monotherapy, or to combination amlodipine (5 mg) and benazepril (20 mg) treatment for 22 weeks. Arterial distensibility was assessed using the DynaPulse ambulatory system, and left ventricular mass was assessed by echocardiography. RESULTS: Combination therapy (0.71% +/- 0.51% mL/mm Hg) increased arterial distensibility more than amlodipine (0.28% +/- 0.69% mL/mm Hg; P =.008) or benazepril (0.39% +/- 0.62% mL/mm Hg; P =.03) monotherapies. Left ventricular mass decreased more with combination treatment (65 +/- 56 g) than with amlodipine (28 +/- 4 g; P <.02); the difference from benazepril (42 +/- 50 g) was not significant. CONCLUSIONS: Combined ACE inhibitor and CCB treatment was more efficacious than high doses of the individual agents in increasing arterial compliance and reducing left ventricular mass. These findings indicate that appropriately selected combinations of antihypertensive drugs might have enhanced cardioprotective effects.     

Telmisartan, an angiotensin II type 1 receptor blocker, improves coronary microcirculation and insulin resistance among essential hypertensive patients without left ventricular hypertrophy

Hypertension and insulin resistance are associated with reduced coronary vasodilatory capacity, possibly caused by structural changes in the coronary resistance vessels. The goal of this study was to compare the effect of an angiotensin receptor blocker (ARB) with that of a calcium channel blocker (CCB) on coronary flow reserve and insulin resistance among essential hypertensive patients without left ventricular hypertrophy. A total of 40 consecutive essential hypertensive patients were randomized to daily 40 mg telmisartan or 20 mg nifedipine coat-core treatment. Coronary flow velocity reserve (CFVR) measurement using transthoracic Doppler echocardiography and blood tests were performed before and after 12 weeks of treatment. At baseline, blood pressure, CFVR, and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly different between the two groups. At the end of the treatment period, the telmisartan and nifedipine groups exhibited similar declines in blood pressure. CFVR was improved in the telmisartan group (2.4+/-0.4 to 2.9+/-0.4; p<0.01), but there was no difference in the nifedipine group (2.5+/-0.3 to 2.5+/-0.3; n.s.). HOMA-IR was improved in the telmisartan group (3.1+/-1.1 to 1.6+/-0.7; p<0.01), but there was no difference in the nifedipine group (2.8+/-1.1 to 2.4+/-0.7; n.s.). In conclusion, this study demonstrates that antihypertensive therapy with telmisartan, but not nifedipine, has a beneficial effect on coronary microcirculation and insulin resistance among essential hypertensive patients.     

Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: Focus on felodipine

Summary Calcium entry through L-type calcium channels is essential for contraction of both arterial smooth muscle and the myocardium, and is important in cardiac conduction. First-generation calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac function at doses producing therapeutic arterial dilatation. Such agents may cause deterioration in patients with left ventricular dysfunction, and their combination with a beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agents has focused on obtaining a higher degree of vascular selectivity. Felodipine is a highly vascular selective calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally. Isradipine and nicardipine are also vascularly selective calcium entry blockers. Hemodynamic studies in patients with hypertension, coronary artery disease, congestive heart failure, or in patients receiving beta-adrenergic blockade, show that felodipine can produce profound arteriolar dilatation without the negative effects of left ventricular systolic performance. Furthermore, felodipine alone or when added to a beta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of dihydropyridine calcium entry blockers in hypertension and angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their effect from inhibition of cardiac performance. As some of these patients, most commonly the elderly, have concomitant left ventricular dysfunction, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients with heart failure indicate that felodipine and amlopidine may improve hemodynamics, reduce neurohormonal activation, and increase exercise tolerance, but final conclusions must await the randomized clinical trials now underway.     

The incidence of prebypass dysrhythmias in patients undergoing coronary artery surgery

The incidence of dysrhythmias during the prebypass period of coronary artery surgery has not been accurately reported. Using Holter monitoring of the electrocardiogram, this study was undertaken to determine the incidence of dysrhythmias and ischemia and their relationship to specific events during the prebypass period. The role of preoperative calcium entry blockers (CEB), beta-adrenergic blockers (BB), or both on the incidence of dysrhythmiss and ischemia was also studied. One hundred thirty-eight patients were premeditated with morphine, scopolamine, and diazepam. Anesthesia was induced with fentanyl or sufentanil followed by either pancuronium or vecuronium and maintained with sufentanil or enflurane. All 138 patients experienced a dysrhythmia during the prebypass period. Seventy-five percent of the patients had at least one episode of a supraventricular dysrhythmia (SVD), 39% had a sinus bradycardia, and 20% had a conduction abnormality. Ninety-two percent of the patients had premature ventricular contractions (PVC) and, surprisingly, 76% had non-sustained ventricular tachycardia. One patient developed ventricular fibrillation and one had ventricular tachycardia. The peak incidence of dysrhythmias occurred at insertion of the pulmonary artery (PA) catheter and at aortic dissection. The incidence of prebypass ischemia was 18%, but these patients did not have a higher incidence of ventricular dysrhythmias. Preoperative CEBs and BBs did not influence the incidence of ischemia or dysrhythmias with the exception of SVD; there was a significantly lower incidence at PA catheterization in patients taking CEBs preoperatively (P < .05). It can be concluded that dysrhythmiss are very common during the prebypass period. The low rate of progression to life-threatening dysrhythmias may be related to the fact that the majority occurred during mechanical stimulation and that patients were chronically taking CEBs and/or BBs preoperatively.