Albert A. Carr

Magnetic resonance imaging compared to echocardiography to assess left ventricular mass in the hypertensive patient.

Echocardiography (ECHO) is useful to document changes in left ventricular mass (LVM) in groups of patients, but may be too variable for use in the individual patient. Magnetic resonance imaging (MRI) may be a more precise and reliable method to quantify the mass of the left ventricule. This study reports the accuracy, precision, and reliability of LVM estimates by MRI as compared to data obtained by ECHO in hypertensive patients. Accuracy referred to the comparison of LVM by MRI to anatomical LVM determined by autopsy. Precision was examined using 34 duplicate MRI images and by blindly reading 24 duplicate M-mode strips. Reliability was assessed by MRI in four subjects over 2 months, and by ECHO in 22 hypertensive patients over 2 weeks. Agreement between MRI and ECHO estimates of LVM was determined in the same 17 hypertensive patients using linear regression. MRI LVM estimates were within 17.5 g (95% CI) of the true LVM. The linear agreement between MRI and ECHO estimates of LVM could be described by the equation MRI = 0.61 x ECHO + 49.57 (r = 0.63, P < .01). The precision of LVM by MRI (11 g) was over twice that observed with ECHO (26 g). The reliability of MRI LVM estimates was more consistent (+/- 8 g) than that for ECHO (+/- 49 g). MRI appears to be a more precise and reliable method for measuring LVM, and would be more suitable than ECHO for the clinical evaluation of the individual patient.

Relation among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease

Abstract Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallum-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or coronary artery disease. Abnormal vasodilator reserve (ratio The decrement in flow reserve was not linearly related to the of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detetable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease, Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects. Depressed coronary reserve is typically found in hypestensive patients with hypertrophy and increased basal coronary flow velocity, but less typical presentations including hypertrophy and normal or low coronary low velocity are found in advanced hypertensive disease.

Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension

Eplerenone is a highly selective aldosterone blocking agent, which was recently approved for the treatment of hypertension and has also been shown to reduce mortality in post-myocardial infarction patients with heart failure. To assess its usefulness in patients with essential hypertension, we performed a 12-week, double-blind, placebo-controlled, parallel-arm, fixed-dose study over a range of doses using clinic and ambulatory blood pressure (BP). After single-blind placebo therapy for 3 to 4 weeks to obtain baseline measures, 400 patients were randomized to receive placebo or 1 of 4 doses of eplerenone (25, 50, 100, and 200 mg once daily). In addition, changes from baseline in serum potassium, active renin activity, and serum aldosterone were assessed. After 12 weeks of therapy, reductions in clinic BP showed a significant dose response in which 25 mg of eplerenone achieved statistical significance compared with placebo for systolic BP; maximum clinic BP reduction was achieved with the 100 mg dose. Ambulatory BP monitoring showed that all doses of eplerenone (25 to 200 mg/day) lowered BP significantly greater than placebo with a significant dose response. The 24-hour mean BP reductions ranged from 6.4/4.4 to 10.3/5.7 mm Hg on eplerenone compared with 1.3/0.8 mm Hg on placebo. One patient on placebo and 1 patient on 200 mg of eplerenone had episodes of elevated serum potassium levels (>5.5 mEq/L). Increases in serum aldosterone were related to dose but not to reductions in 24-hour BP. Side effects and withdrawal rates attributed to eplerenone were similar to those of placebo. These data show that eplerenone is an effective antihypertensive agent at doses as low as 25 mg/day. The top effective dose in stage 1 to 3 hypertension based on clinic and ambulatory BP was 100 mg once daily. The incidence of elevated serum potassium levels was not increased across doses of eplerenone in this study.

Low-dose drug combination therapy: An alternative first-line approach to hypertension treatment

To investigate the concept that the initial treatment of hypertension with low doses of two antihypertensives that have different modes of action and additive effects may achieve control of blood pressure and minimize the dose-dependent adverse effects seen with conventional monotherapy, a randomized, double-blind parallel group dose-escalation study was conducted. After a 4 to 5 week placebo washout period, 218 men and women with diastolic blood pressure between 95 and 114 mm Hg were randomly allocated to take: amlodipine (2.5 to 10 mg), enalapril (5 to 20 mg), and the low-dose combination of bisoprolol (2.5 to 10 mg) with 6.25 mg of hydrochlorothiazide (HCTZ). All drugs were administered once daily, titrated to optimal response, and taken for a total of 12 weeks. Blood pressure was measured 24 hours after dose. The response rates (either a diastolic blood pressure < or = 90 mm Hg or a decrease of diastolic pressure > or = 10 mm Hg) were 71% for bisoprolol-6.25 mg HCTZ, 69% for amlodipine, and 45% for enalapril. The mean decreases in systolic/diastolic blood pressure from baseline were 13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolol-6.25 mg HCTZ, amlodipine, and enalapril, respectively. The mean change with enalapril was less than the other drugs (p < 0.01), although the once-daily dosing of enalapril and the maximum dose of 20 mg might not have been optimal for this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Losartan: First of a New Class of Angiotensin Antagonists for the Management of Hypertension

Angiotensin receptor antagonists represent a new class of drugs for the treatment of patients with hypertension. Reduction of blood pressure in patients with essential hypertension requires increased activity of the renin—angiotensin system. Losartan, the first orally active, nonpeptide angiotensin antagonist, specifically competes with angiotensin II (Ang II) for the AT1 receptor and reversibly alters the receptor. Maximum blood pressure reductions occur after doses of approximately 50 mg, although some patients will require 100 mg; the parent compound and a metabolite are responsible for a smooth 24‐hour effect on blood pressure. Once‐daily dosing with losartan has been documented to be safe. The drugs safety has been evaluated in 4,058 patients; of these patients, more than 1,200 were treated for longer than 6 months and more than 800 were treated for longer than 1 year with doses of 10 mg to 150 mg. Overall, no hypertensive patients were withdrawn from treatment because of elevated serum creatinine or potassium levels, and there were no reports of angioedema. In addition, some reductions in plasma uric acid levels were noted. Cough occurred significantly less often in patients treated with losartan than in those treated with hydrochlorothiazide or lisinopril. In contrast to angiotensin‐converting enzyme (ACE) inhibitors, losartan does not activate bradykinin—nitric oxide—prostanoid vasodilation.

A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study to Assess the Efficacy and Safety of Nebivolol, a Novel β-Blocker, in Patients With Mild to Moderate Hypertension

This double‐blind, multicenter, randomized placebo‐controlled study evaluated the antihypertensive efficacy and safety of nebivolol, a selective β1‐adrenoreceptor blocker with vasodilating effects, in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] ≥95 mm Hg and ≤109 mm Hg). A total of 909 patients were randomized to receive placebo or nebivolol 1.25, 2.5, 5, 10, 20, or 40 mg once daily for up to 84 days. The primary end point was the change in trough SiDBP from baseline to study end. Nebivolol significantly reduced trough SiDBP (8.0–11.2 mm Hg compared with 2.9 mm Hg with placebo; P<.001) and trough sitting systolic blood pressure (a 4.4–9.5‐mm Hg decrease compared with a 2.2‐mm Hg decrease with placebo; P≤.002). The overall adverse event experience was similar in the nebivolol (46.1%) and placebo (40.7%) groups (P=.273). Once‐daily nebivolol is an effective antihypertensive in mild to moderate hypertensive patients.

Heterogeneous Vasomotor Responses of Coronary Conduit and Resistance Vessels in Hypertension

OBJECTIVES The purpose of our study was to investigate the relation between conductance and resistance coronary vasomotor responsiveness in hypertensive patients without atherosclerosis. BACKGROUND Although similar in morphology, conduit and resistance coronary vessels differ importantly in size, function and local environment and appear to be differentially affected in certain disease processes, such as atherosclerosis and hypertension. However, little is known about the effect of hypertension on contiguous coronary conduit and resistance vessels in humans. METHODS Changes in coronary blood flow (a measure of resistance vessel reactivity) and coronary artery diameter (a measure of conduit vessel reactivity) were investigated in response to graded infusion of the endothelium-dependent agonist acetylcholine (ACh) in 98 patients with normal coronary arteries. RESULTS In 31 normotensive, euglycemic patients, conduit and resistance coronary artery responses to intracoronary infusion of ACh were significantly correlated (r = 0.73, p = 1 x 10[-6]), although eight patients (26%) had constriction of conduit but dilation of resistance arteries at peak effect. In 28 hypertensive patients without left ventricular hypertrophy (LVH), conduit and resistance artery responses to ACh remained significantly correlated (r = 0.5, p = 0.006), although 12 patients (43%) had discordant findings. Finally, in 39 hypertensive patients with LVH, conduit and resistance artery responses to ACh displayed the lowest correlation (r = 0.38, p = 0.02), with 22 patients (56%) demonstrating conduit artery constriction and resistance artery dilation. CONCLUSIONS Despite angiographically normal coronary arteries, heterogeneous vasomotor responses (dilation and constriction) were demonstrated in contiguous conduit and resistance arteries in normotensive and hypertensive patients referred for cardiac catheterization because of chest pain. In addition to more severe endothelial dysfunction among conduit and resistance arteries, a greater frequency of discordant conduit and resistance artery responses and resistance vessel constriction was found with increasing severity of hypertension. Our study suggests differing mechanisms of endothelium responsiveness to ACh among conduit and resistance coronary arteries.

Effect of African-American Race and Hypertensive Left Ventricular Hypertrophy on Coronary Vascular Reactivity and Endothelial Function

Excess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we subjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase in coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorical and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertrophy. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and dilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxation during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy.

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine☆

OBJECTIVES The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. BACKGROUND Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. METHODS Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. RESULTS In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. CONCLUSIONS We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.

How can we diagnose coronary heart disease in hypertensive patients

Chest pain is a common complaint among hypertensive patients. Hypertension and coronary heart disease each may present with symptoms and signs that are clinically indistinguishable. Noninvasive testing by routine exercise stress testing and stress radionuclide angiography are not reliably predictive of ischemia resulting from obstructive epicardial coronary artery disease and should be abandoned for that diagnostic purpose. Noninvasive thallium-201 myocardial perfusion imaging for this purpose may prove to be a valuable tool, avoiding the risk and expense of coronary arteriography. However, carefully performed prospective studies are not available. Because of the high prevalence of both diseases, a high priority must be given to obtaining these data and evaluating other noninvasive methods (especially positron emission tomography) if they appear promising.