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Dihydropyridine and nondihydropyridine calcium channel blockers (CCB) differ in pharmacologic characteristics. Few clinical studies distinguish effects of CCB as monotherapy. We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension. Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were randomly assigned to either nifedipine-GITS or verapamil-SR. Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks. Clinic blood pressure (BP), 24-h ambulatory BP, exercise BP, left ventricular mass, systolic and diastolic function by echocardiography, and coronary flow reserve by split-dose thallium-201 imaging with adenosine were assessed at baseline, end of titration, 3 months and 6 months of treatment. Plasma renin activity, atrial natriuretic peptide, norepinephrine, and epinephrine were assayed. Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index. Compared to nifedipine-GITS, verapamil-SR produced a significantly lower resting and peak exercise heart rate. Nifedipine-GITS elicited a lower peak exercise systolic BP. At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels, no longer apparent by 6 months. Plasma norepinephrine was lower with verapamil-SR, also at end titration and at 3 months, but not at 6 months. Plasma epinephrine and plasma renin activity were unchanged by either drug. There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments. Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension. Differences in their hemodynamic profiles and neurohormonal responses are consistent with preclinical pharmacologic characteristics. The clinical implications of their similarities and differences remain to be fully evaluated in outcome studies.

Recent evidence suggests that regression of left ventricular hypertrophy (LVH) with antihypertensive therapy improves prognosis. The mechanism for this benefit is unknown but may be related to effects on myocardial performance. Midwall fractional shortening (mFS) is often depressed in patients with asymptomatic hypertension, is associated with LVH, and is a potent, independent predictor of outcome. We therefore examined whether antihypertensive therapy may improve midwall performance. mFS as well as conventional echocardiographic parameters were measured serially among 29 hypertensive persons during 6 months of drug therapy. Stress-adjusted and absolute midwall function improved by 10% and 11%, respectively (p <0.05), whereas no significant changes were detected in other measures of chamber function. Improvement in function was more pronounced in patients with concentrically remodeled ventricular geometry and in those who achieved greater reductions in left ventricular (LV) mass. Antihypertensive therapy and LV mass regression is associated with demonstrable improvements in cardiac performance when assessed using mFS. Determinations of mFS may have a promising role in identifying patients with early hypertensive heart disease, tracking responses to therapy, and in elucidating the potential beneficial effects associated with LV mass regression.

Background: The pressor response to examination in the clinic setting is called the 'white coat effect' (WCE). This response may be a confounder when investigators use clinic blood pressure as a measure of response to antihypertensive therapy., Objective: ;To study the effect of the pressor response by evaluating the sex-specific effect of treatment with calcium antagonism on blood pressure measured in the clinic and by ambulatory blood pressure monitoring (ABPM)., Methods: Untreated hypertensive subjects (n=39) with seated clinic diastolic blood pressures (DBP) > or = 100 and < or = 130mmHg were studied. Same-day clinic systolic blood pressure (SBP) and ambulatory SBP were obtained after 1 week of placebo, and after 1 month of treatment with either nifedipine or verapamil in a randomized, blinded, parallel trial., Results: With placebo, women s average SBP was 18+/-;4mmHg lower than clinic SBP. By contrast, men s average SBP with placebo was 4+/-15mmHg lower than clinic SBP. There was a significantly greater reduction in clinic SBP for women than there was for men after 1 month of treatment (by 33+/-13 versus 18+/-18mmHg, P<0.005). However, reduction in ambulatory SBP after 1 month was the same for both sexes (20+/-11 versus 19+/-12mmHg)., Conclusions: In this study of moderate-to-severe hypertensives, the large WCE measured for women, which markedly diminished with treatment, accounts for the observed sex difference in response of clinic SBP to calcium antagonism. By contrast, with ABPM there was an equivalent response to treatment for both sexes. Use of ABPM could be a valuable means of eliminating the WCE as a confounder in clinical research.

Clinic blood pressure measurements have only limited ability to determine which hypertensive patients are at greatest risk of cardiovascular events. Ambulatory blood pressure monitoring allows for noninvasive measurement of blood pressure throughout the 24-hour period. This may help to clarify discrepancies between blood pressure values obtained in and out of the clinic and confirm the presence of white-coat hypertension, broadly defined as an elevated clinic blood pressure but a normal ambulatory blood pressure. Ambulatory blood pressure values have been shown to have a better relationship to cardiovascular morbidity and mortality and end-organ damage than clinic blood pressure values. Further, patients with white-coat hypertension appear to be at greater risk of cardiovascular morbidity and end-organ damage than a normotensive population, although they are at less overall risk than a hypertensive population. Hypertensive heart disease is characterized by diastolic dysfunction, increased left ventricular mass, and coronary flow abnormalities. Left ventricular hypertrophy increases the risk of coronary heart disease, congestive heart failure, stroke, ventricular arrhythmias, and sudden death. A variety of invasive and noninvasive techniques are described herein that measure left ventricular mass, diastolic function, and coronary blood flow abnormalities. Most antihypertensive treatments promote regression of left ventricular hypertrophy and reversal of diastolic dysfunction, which may decrease symptoms of congestive heart failure and improve survival.

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Conventional measures of left ventricular (LV) systolic performance suggest that diastolic dysfunction precedes the development of systolic dysfunction in hypertension. Midwall fractional shortening is a new measure of systolic function that identifies hypertensive patients who have evidence of target-organ damage, impaired contractile reserve, and increased mortality. We therefore sought to determine whether depressed midwall fiber shortening is associated with abnormal diastolic function. Echocardiograms were obtained in 102 otherwise healthy hypertensive patients without treatment with normal conventional measures of systolic function. Of these, 15 had depressed midwall shortening based on previously described normative relations. Patients with depressed midwall shortening had slightly higher blood pressure. Abnormal diastolic function, defined as late (A) LV inflow velocity greater than early (E) velocity, was observed in 33% of those with normal midwall shortening but in 60% of those with depressed shortening (p <0.05). Patients with A/E >1 had lower absolute midwall fiber shortening (15 +/- 3% vs 18 +/- 3%, p <0.0001) but similar endocardial shortening. Patients with abnormal midwall shortening had higher A/E and longer isovolumic relaxation times (both p <0.05). In multivariate analysis, midwall fractional shortening, age, and heart rate were independent predictors (p <0.01) of A/E in a model including blood pressure, LV mass, and endocardial shortening. We conclude that subnormal midwall shortening predicts LV diastolic abnormalities in this population of hypertensive patients with otherwise normal measures of LV systolic function. Contrary to our previous understanding, depressed LV systolic performance, when identified with this newer method, occurs coincidentally with impaired diastolic function.

We evaluated the impact of diastolic function and gender on exercise capacity in sedentary, untreated hypertensive subjects (34 men, 23 women) using echocardiography and a bicycle ergometry with measurement of oxygen consumption (VO2). In men, peak (A) mitral inflow velocity and left ventricular (LV) mass were inversely related to peak VO2 (r = -0.64) and maximal workload (r = -0.57) and were the sole independent determinants of exercise capacity. In women, there was no relationship between any echocardiographic measure and exercise capacity. Thus, LV mass and Doppler-determined diastolic function predict maximal VO2 in hypertensive men but not in women. This finding may be related to gender differences in the contribution of diastolic filling to exercise capacity or may reflect limitations of resting Doppler echocardiography to predict exercise diastolic filling in hypertensive women.

Objective: We sought to determine whether a prolonged QRS-interval duration is associated with decreased left ventricular (LV) systolic function., Background: The 12-lead electrocardiogram (ECG) is a routine test for suspected cardiac disease. Although several scoring systems have been devised to estimate LV systolic function, no studies have examined the direct relationship between QRS duration alone and LV systolic function., Methods: We analyzed the standard 12-lead surface ECG of 270 consecutive patients, referred for radionuclide ventriculography. Patients (n = 44) with bundle branch blocks, atrial flutter or fibrillation, pacemaker rhythm, recent myocardial infarction or bypass surgery, and patients on antiarrhythmic drugs were excluded. In the remaining patients (n = 226), we correlated the QRS duration on standard resting ECG, and the resting LV ejection fraction (EF), end-systolic and end-diastolic counts (ESC and EDC, respectively; LV volume indices), as obtained by radionuclide angiography. We used a multivariate analysis to identify independent predictors of reduced ventricular function entering QRS duration, the previously described R-wave score and clinical variables in our model., Results: The QRS duration in the abnormal EF group was significantly longer than in the normal EF group (0.102 vs. 0.091 s, p < 0.0001). A QRS duration >0.10 s was highly specific (83.6%), but modestly sensitive (43.8%), for the prediction of abnormal EF. Furthermore, an abnormal EF was predicted with incrementally increased specificity (83.6% to 99.3%) and a corresponding decrease in sensitivity (43.8% to 13.8%) for each 0.01-s increase in the definition of prolonged QRS (from >0.10 to >0.12 s). Accordingly, the positive likelihood ratio for the prediction of decreased LV function was increased from 2.67 to 19.7 as the definition of prolonged QRS duration was increased from >0.10 to >0.12 s. In the multivariate analysis, a prolonged QRS duration and a low R-wave score were the only independent predictors of decreased LV systolic function., Conclusions: Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is a specific, but relatively insensitive indicator of decreased LV systolic function. Further prolongation of the QRS had a higher specificity for decreased LV EF and a higher positive likelihood ratio for predicting abnormal LV EF.

Compared to office measurements, ambulatory monitoring is a more accurate method of blood pressure (BP) characterization and may therefore be useful in a genetics study of hypertension. We studied the relation between the M235T polymorphism of the angiotensinogen gene and hypertension using office and ambulatory (BP) measurements. We enrolled untreated subjects (33 men and 17 women) who were referred for evaluation of office BP >140/90 mm Hg on at least two separate occasions. The M235T genotypes of the angiotensinogen gene were determined by polymerase chain reaction (PCR) amplification of DNA extracted from peripheral blood leukocytes and digested with BSTU1. The distribution of the genotypes were MM = 0.22, MT = 0.44, TT = 0.34. Based on office measurements, a significant difference in diastolic blood pressure (BP) was detected only between the TT and the MT genotype subjects (office BP: MM = 150 +/- 25/97 +/- 13 mm Hg, MT = 147 +/- 23/ 95 +/- 13 mm Hg, TT = 161 +/- 25/104 +/- 15 mm Hg). By contrast, with ambulatory BP monitoring, both systolic and diastolic blood pressures were significant higher in TT versus MM and MT (ambulatory BP, MM = 138 +/- 10/88 +/- 9 mm Hg, MT = 141 +/- 15/89 +/- 11 mm Hg, TT = 152 +/- 18/97 +/- 12 mm Hg). Covariate analysis revealed an independent relationship between the M235T genotype and systolic, diastolic, and mean ambulatory BP. Ambulatory monitoring improved the analytic power of our study and allowed detection of a clear and consistent relationship between angiotensinogen polymorphism and hypertension with a relatively small sample size.

The purpose of this study was to assess several indexes of cardiovascular risk in men and women with moderate to severe hypertension. We found that women with moderate and severe hypertension have lower ambulatory blood pressure and less cardiac hypertrophy than men with similar clinic blood pressure.

Achieving low interobserver variability is a goal of echocardiographic determined left ventricular (LV) mass measurements. In a group of hypertensives, we evaluated interobserver variation using a method of simultaneously acquired two-dimensional (2-D) cine and M-mode images displayed in a split screen format. Sixty echocardiographic images from ongoing hypertension trials, including serial studies of the same patients, were obtained with an UltraMarktrade mark 6 Ultrasound System (Advanced Technology Laboratories, Inc., Bothell, WA, USA). Images were digitized online, coded with a random number, and pooled prior to the analysis to minimize observer bias. Studies were read by two independent observers in a blinded fashion and in a random order using a Color Vue II Nova MicroSonicstrade mark analyzer (Nova Microsonics, Mahwah, NJ, USA). The M-mode tracing and cine of three consecutive frames of 2-D parasternal short-axis views of the LV were simultaneously displayed in a split screen format. The 2-D cine was used as a reference image during M-mode measurements of LV dimensions. Measurements were obtained and the LV mass estimated according to the Penn convention. Interobserver variability for left ventricular internal dimension (LVID), interventricular septal thickness (IVS), posterior wall thickness (PWT), and left ventricular mass (LV mass) is low when either correlated (Pearson correlation coefficients of 0.94, 0.82, 0.75, and 0.93, respectively) or expressed as a percent of the mean (3.0%, 10.0%, 10.2%, and 8.9%, respectively). When read in a blinded fashion, interobserver variability (especially for LV mass) is small using digitized, simultaneously acquired and displayed cines of 2-D and M-mode echocardiograms. This is likely due to the ability to discriminate myocardial wall edges (endocardium) from other associated structures such as tricuspid and mitral apparatus. This method may prove useful in studies of LV mass.

An insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with myocardial infarction, cardiomyopathy, and left ventricular (LV) hypertrophy. LV mass and geometry are related to cardiovascular morbidity and mortality. Two-dimensional directed M-mode echocardiograms and 24-hour ambulatory blood pressure monitoring were performed in 67 hypertensive subjects. Echocardiographic measurements were assessed in blinded fashion. LV mass index and relative wall thickness were calculated. ACE genotypes were determined by polymerase chain reaction amplification of deoxyribonucleic acid prepared from leukocytes, using primers that encompass the polymorphic segment. Systolic ambulatory blood pressure was higher in subjects with the II genotype. All other patient characteristics were similar across genotype groups. After adjustment for other covariables, the DD and ID genotypes were associated with significantly higher LV mass index than was the II genotype. Adjusted relative wall thickness was also higher in subjects with the DD genotype than in subjects with the ID and II genotypes. On multiple regression analysis, systolic ambulatory blood pressure, gender, body mass index, and the ACE genotype were each independently related to LV mass index (R2 = 0.53). Systolic ambulatory blood pressure, race, and ACE genotype were each independently related to relative wall thickness (R2 = 0.34). The ACE genotype explained an additional 3% and 4% of the variations of LV mass index and relative wall thickness, respectively. In conclusion, ACE polymorphism accounted for a small but statistically significant proportion of the variation in LV mass and geometry in our hypertensive subjects.

Background: Thallium-201 stress imaging is the most often used noninvasive test for detection of coronary artery disease. Its utility in patients with end-stage lung disease has not been defined., Methods: Feasibility, safety, and reliability of thallium 201 perfusion imaging was evaluated in 23 consecutive candidates for lung transplantation. All underwent graded dobutamine thallium 201 single photon emission computed tomography imaging. The perfusion imaging results were correlated with results of coronary angiography, radionuclide angiography, and right heart catheterization., Results: The testing was completed without complications in all patients. No perfusion abnormality was detected in five patients, and none had evidence of coronary artery disease on coronary angiography. In 18 patients with abnormal thallium 201 imaging, coronary artery disease was detected in four patients only, and no angiographic data was available in three patients. Thus, in at least 11 of 23 patients, thallium 201 imaging was falsely positive. There was a trend toward lower left ventricular ejection fraction in patients with abnormal thallium 201 imaging. No correlation was found between thallium 201 results, pulmonary artery and right atrial pressures at rest. Possible noncoronary origin of the perfusion defects include the following (1) presence of sarcoid in the myocardium, (2) left ventricular attenuation by hypertrophied right ventricle, and (3) altered left ventricular anatomy, function, and coronary perfusion as a result of right ventricular pressure overload., Conclusions: Dobutamine thallium 201 stress test can be safely performed in lung transplant candidates. However, its specificity for detection of coronary artery disease is low. Selective use of coronary angiography in patients with multiple risk factors is likely a more cost-effective approach.