Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry.

BACKGROUND/INTRODUCTION: The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. METHODS: In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m2; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. RESULTS: Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 and -29/-12 mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9 mmHg, respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10-mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24-h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. CONCLUSIONS: In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.

Enhancing activity of various immunoaugmenting agents on the delayed-type hypersensitivity response in mice.

Six immunoaugmenting agents were tested in the delayed-type hypersensitivity reaction (DTH) in normal BALB/c X DBA/2 mice. The agents tested, levan, lentinan, mannozym, maleic anhydride divinyl ether, polyriboinosinic-polycytidylic acid-poly-L-lysine, and highly purified L-cell interferon, gave significant increases in the DTH response above the sheep red blood cell control. The schedule of doses for each agent corresponded with previous experiments from this laboratory of the maximum natural killer cell activity, macrophage activation, and interferon induction. Highly purified L-cell interferon was capable of eliciting a significant DTH response when given 4 hr after the initial challenge with sheep erythrocytes. In addition, lambda-carrageenan, a macrophage-cytotoxic agent which can render the macrophage inactive, was found to suppress the DTH response to levels slightly above phosphate-buffered saline controls. The carrageenan-induced suppression of the DTH response could be abrogated by coadministration with immunoaugmenting agents to levels attained with the immunoaugmenting agents alone.

Long-term effects of multielectrode renal denervation on cardiac adaptations in resistant hypertensive patients with left ventricular hypertrophy.

Left ventricular (LV) hypertrophy and diastolic dysfunction predict long-term cardiovascular events. We evaluated whether multielectrode renal denervation (RDN) can provide beneficial cardiac adaptations in patients with resistant hypertension and LV hypertrophy long term at 24 months. Seventeen patients with true drug-resistant hypertension (age: 57±9 years, 11 men, body mass index: 33.79±5.49 kg m-2, office blood pressure (BP): 183±20/97±18 mm Hg and ambulatory BP: 152±16/86±15 mm Hg receiving 4.5 anti-hypertensive drugs per day) and LV hypertrophy underwent multielectrode RDN (EnligHTNTM, St Jude Medical). At baseline, LV mass index averaged 141.1±16.8 g m-2 (58.4±7.8 g m-2.7) and mitral lateral E/E' 14.7±6.2. At 6, 12 and 24 months after RDN, the LV mass/body surface area (LV mass per height2.7) reduced significantly by 9.1% (8.8%), 11.3% (10.5%) and 15.5% (14.1%), respectively; and the mitral lateral E/E' reduced significantly by 14.0%, 15.3% and 29.7%, respectively. At 24 months after RDN, majority (70.6%) of the patients showed regression of LV hypertrophy of at least one level; the proportion of patients with concentric LV hypertrophy had dropped by 47.1% from baseline; and the proportion of patients with office systolic BP level of ⩾160 mm Hg had dropped by 76.5% from baseline. No statistically significant association was observed between the changes in office BP and the changes in LV mass index or diastolic function. In patients with drug-resistant hypertension and LV hypertrophy, multielectrode RDN can contribute to significant and sustained improvements of diastolic dysfunction and attenuation of LV mass indices long term at 24 months.

Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT).

BACKGROUND: A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. METHODS AND RESULTS: Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P=0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol. CONCLUSIONS: In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.

Cardiorespiratory fitness and coronary heart disease risk factor association in women.

OBJECTIVES: The purpose of this study was to examine the association between cardiorespiratory fitness and coronary risk factors in healthy, nonsmoking adult women. BACKGROUND: A sedentary life-style is recognized as an independent risk factor for coronary heart disease, and increasing physical activity is strongly recommended to reduce this risk. However, studies examining the effects of increased physical activity on coronary heart disease risk factors in women are relatively few, and the findings have been equivocal. METHODS: Subjects provided written informed consent, completed a questionnaire on medical history and performed an exercise tolerance test. Blood chemistry and lipid levels were determined from fasting blood samples. Three fitness categories were established on the basis of treadmill time to exhaustion and were adjusted for age. RESULTS: The women in the lowest fitness category had less favorable lipid profiles, blood glucose levels, blood pressures and anthropometric indexes than those in the moderate and high fitness categories. CONCLUSIONS: Moderate fitness (equivalent to 10 metabolic equivalents [METs]) is required to improve the coronary risk profile in women.

Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses.

OBJECTIVES: This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography. BACKGROUND: Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age 59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure. RESULTS: Mental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rdeltaSBP = -0.26, rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group.

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.

Effectiveness of potassium chloride or triamterene in thiazide hypokalemia.

Potassium chloride was compared with triamterene in a crossover trial involving 16 hypertensive patients with overt diuretic-induced hypokalemia. Potassium chloride, 24 to 96 mEq/day, normalized the plasma potassium (PK) level at 3.5 mEq/L or more in only eight of the patients. The average increase in PK level was 0.58 mEq/L. Triamterene, 50 to 200 mg daily, normalized PK level in ten of the patients. The average increase in PK level was 0.72 mEq/L, which was not significantly different than that with potassium therapy. Some patients who responded to potassium did not respond to triamterene, and vice versa. Most of the administered potassium was excreted in the urine even with persisting hypokalemia. Addition of triamterene to diuretic therapy resulted in a small but statistically significant increase in plasma creatinine level.

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.

Incidence and cardiac effects of systemic venous air embolism. Echocardiographic evidence of arterial embolization via noncardiac shunt.

Central nervous system dysfunction in venous air embolism may result from air entering the arterial circulation. Using two-dimensional and pulsed-wave Doppler echocardiography, this study not only documented the frequent presence of air in the right heart chambers of patients undergoing upright neurosurgery or pacemaker insertion, but also documented the presence of air in the left atrium and left ventricle of one patient via noncardiac shunt. Studies in dogs confirmed paradoxical air embolism in the absence of anatomic communications between right and left heart chambers. Systemic venous air also produced a dose-dependent increase in pulmonary artery pressure and diastolic flattening of the ventricular septum with increase in left ventricular filling pressure despite preserved systolic function.

Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men. A dose-response relationship.

OBJECTIVE: To examine the association between miles run per week and high-density lipoprotein cholesterol levels in healthy middle-aged men. BACKGROUND: Regular exercise increases levels of high-density lipoprotein cholesterol. However, the exercise requirements for such increases are not well defined. METHODS: Healthy, nonsmoking men (n = 2906; age, 43 +/- 4 years) completed a questionnaire on health habits and physical activities and a symptom-limited exercise test. They were then stratified on the basis of the number of miles run per week. Six groups, with mileages of 0, 5, 9, 12, 17, and 31 per week, were established. RESULTS: A gradual increase in high-density lipoprotein cholesterol level was observed with increased miles (0.008-mmol/L [0.308-mg/dL] increase in high-density lipoprotein cholesterol level per mile). Most of the changes were associated with distances of 7 to 14 miles per week. Levels of low-density lipoprotein cholesterol, triglycerides, and the ratio of total cholesterol to high-density lipoprotein cholesterol also improved with weekly mileage. The high-density lipoprotein cholesterol level correlated significantly with all exercise components, anthropometric measures, and alcohol consumption. Group comparisons disclosed significant differences (P < .05) in exercise time to exhaustion, miles run per week, body fat, body weight, and body mass index. Age and alcohol consumption were similar across groups. CONCLUSIONS: These results indicate a dose-response relationship between miles run per week, high-density lipoprotein cholesterol level, and other lipoprotein-lipid levels. Most changes were noted in those who ran 7 to 14 miles per week at mild to moderate intensities. A mile-age threshold for changes in high-density lipoprotein cholesterol level was not observed. However, when compared with those of the nonexercising group, high-density lipoprotein cholesterol levels attained statistical significance at 7 or more miles per week.

Efficacy and safety of pravastatin in African Americans with primary hypercholesterolemia.

BACKGROUND: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia. METHODS: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio. RESULTS: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%. CONCLUSION: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.

Acute and short-term effects of new calcium antagonist in hypertension.

Nitrendipine (Bay e 5009) is a new calcium antagonist antihypertensive agent similar in structure and function to nifedipine. Nitrendipine was tested in a range of single and repeated doses in 10 adult males with uncomplicated mild to moderate hypertension. The treatment goal was reduction of diastolic blood pressure to 90 mm Hg or less. The dose that achieved goal blood pressure ranged between 10 and 30 mg. Systolic and diastolic blood pressure began to fall within 15 minutes following ingestion of single oral doses of nitrendipine. The maximum effect of the drug was achieved in 60 to 90 minutes and remained at approximately this level for 6 to 8 hours. The average reduction in supine diastolic was more than twice as great as the fall in systolic blood prere began to fall within 15 minutes following ingestion of single oral doses of nitrendipine. The maximum effect of the drug was acheived in 60 to 90 minutes and remained at approximately this level for 6 to 8 hours. The average reduction in supine diastolic was more than twice as great as the fall in systolic blood pressure. With continuous doses given three times daily, all patients' blood pressures were as low or lower than the maximal effect observed after single doses. The reduction in blood pressure was sustained for the full 3 weeks of treatment. There was a sustained small increase in pulse rate averaging 6 beats/min. The drug was generally well tolerated by most patients. Mild to moderate headache that resolved with continued treatment was the most frequent side effect. This preliminary trial indicates that nitrendipine is an effective antihypertensive agent that merits further study.

Impact of different partition values on prevalences of left ventricular hypertrophy and concentric geometry in a large hypertensive population : the LIFE study.

Left ventricular (LV) hypertrophy and concentric remodeling have been defined by using a variety of indexation methods and partition values (PVs) for LV mass and relative wall thickness (RWT). The effects of these methods on the distribution of LV geometric patterns in hypertensive subjects remain unclear. Echocardiograms were obtained in 941 patients with stage I to III hypertension and LV hypertrophy by ECG. LV mass was calculated by using different methods of indexation for body size and different PVs to identify hypertrophy: LV mass/body surface area (g/m(2)) PV for men/women 116/104, 125/110, or 125/125; LV mass/height (g/m) PV 143/102 or 126/105; and LV mass/height(2.7) (g/m(2.7)) PV 51/51 or 49.2/46.7. RWT was calculated by either 2xend-diastolic posterior wall thickness (PWT)/end-diastolic LV internal dimension (LVID) or end-diastolic interventricular septum dimension+end-diastolic PWT/end-diastolic LVID. LV hypertrophy or remodeling was present in 63% to 86% of subjects, and LV hypertrophy was present in 42% to 77%. By any index, eccentric hypertrophy was the common LV geometric pattern. Use of interventricular septum dimension+PWT/LVID to calculate RWT slightly increased the prevalence of normal geometry and eccentric hypertrophy compared with the use of 2xPWT/LVID. Subjects with LV hypertrophy identified by only LV mass/height(2.7) PV 49.2/46.7 were more obese, whereas those identified by only LV mass/body surface area PV 116/104 were taller and thinner than those in the 2 concordant groups with or without LV hypertrophy by both criteria. By either criterion, there were no significant differences between different LV geometric patterns in clinical cardiovascular disease. Hypertensive patients with LV hypertrophy by ECG have a high prevalence of geometric abnormalities, especially eccentric hypertrophy, irrespective of method of indexation or PV. LV mass indexation by body surface area or height(2.7) identifies lean and obese subjects, respectively. We found no difference in prevalent cardiovascular disease in subjects identified by either criterion, suggesting a similar high risk.

Treatment of severe hypertension with intravenous labetalol.

The effectiveness of repeated intravenous injections of labetalol in reducing blood pressure (BP) was evaluated in patients with severe hypertension. The subjects were 10 patients who were 29 to 61 yr old and who had diastolic blood pressure (DBP) of 125 mm Hg or higher. Repeated injections titrated from 20 to 80 mg were given at 15-min intervals until there was a reduction in DBP of 30 mm Hg or until 300 mg had been administered. The average reduction of BP ranged from 201 +/- 5/132 +/- 1 to 157 +/- 6/108 +/- 4 mm Hg (mean +/- SEM). Four patients responded with a reduction in DBP of 30 mm Hg or more with total doses of 60 to 220 mg. Of the remaining six who received the full dose, in four there was a 20 to 29 mm Hg reduction in DBP, in one there was a 10 mm Hg fall, and in one there was no reduction. There was a positive correlation between age and response to intravenous labetalol. No severe side effects were encountered. Intravenous labetalol is useful and well tolerated in patients with severe hypertension.

Therapeutic adherence in the elderly: transdermal clonidine compared to oral verapamil for hypertension.

This double-blind, double-dummy, randomized clinical trial, conducted in elderly patients with mild hypertension, compared adherence to treatment, efficacy, side effects, and quality of life during treatment with transdermal clonidine versus oral sustained-release verapamil (verapamil-SR). Blood pressure declined significantly--from 148/95 mm Hg at baseline to 139/84 after titration and 135/86 after maintenance--with transdermal clonidine (n = 29), and from 156/96 to 144/85 and 148/88, respectively, with verapamil-SR (n = 29). Adverse event rates and quality-of-life questionnaire responses were similar in the two treatment groups. Transdermal clonidine was worn as directed during more than 96% of patient-weeks of treatment. Compliance with the oral verapamil regimen was less consistent: Verapamil-SR was taken as directed during approximately 50% of patient-weeks of therapy, and individual compliance, assessed by tablet counts, varied from 50-120%. In all, 86% of subjects were satisfied or highly satisfied with the convenience of transdermal therapy; 87% reported that side effects were slightly or not bothersome; 65% indicated that transdermal patches were more convenient than oral therapy; and almost 60% preferred transdermal to oral therapy. In this study transdermal clonidine and oral verapamil were equally safe and effective. A substantial majority of patients preferred transdermal to oral therapy, and adherence to treatment was greater with transdermal therapy.

Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents.

PURPOSE: This multicenter, double-blind, parallel group study assessed the usefulness of the ambulatory blood pressure monitoring (ABPM) technique in differentiating between the once-daily administration of the beta blockers bisoprolol (10 to 20 mg) and atenolol (50 to 100 mg) in terms of efficacy and duration of action. PATIENTS AND METHODS: The study population consisted of 659 patients with essential hypertension and an average office diastolic blood pressure (BP) between 95 and 115 mm Hg after 4 weeks of placebo treatment. Office BPs were recorded at the end of the 24-hour dosing interval (trough). ABPM was performed in 11 of the 28 institutions participating in this study in a total of 203 patients. These procedures were performed at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: With the use of conventionally measured office BPs, the two drugs significantly (p < 0.001) decreased trough systolic and diastolic BPs to a similar extent. By 24-hour monitoring, bisoprolol demonstrated a 33% greater reduction in whole-day average diastolic BP than did atenolol (11.6 +/- 0.7 mm Hg versus 8.7 +/- 0.8 mm Hg, p < 0.01). Significant treatment differences in systolic (p < 0.05) and diastolic (p < 0.01) BPs were also noted for bisoprolol compared with atenolol during the final 4 hours of the dosing interval (-13.2 +/- 1.5/-10.9 +/- 1.0 mm Hg versus -8.9 +/- 1.6/-7.3 +/- 1.1 mm Hg, respectively), and over the time period 6:00 AM to noon (-14.2 +/- 1.3/-11.5 +/- 0.9 mm Hg versus -9.9 +/- 1.4/-7.7 +/- 0.9 mm Hg). CONCLUSIONS: Whereas conventional BP measurements did not detect differences in the antihypertensive effects of the beta blockers bisoprolol and atenolol, ABPM revealed significant treatment differences in both the efficacy and duration of action of these two agents. These findings indicate the power of this technique to discriminate potentially important differences between apparently similar antihypertensive drugs.

Relation of QT interval and QT dispersion to echocardiographic left ventricular hypertrophy and geometric pattern in hypertensive patients. The LIFE study. The Losartan Intervention For Endpoint Reduction.

OBJECTIVE: In hypertensive patients, left ventricular hypertrophy (LVH) predicts increased mortality, in part due to an increased incidence of sudden death. Repolarization-related arrhythmogenesis may be an important mechanism of sudden death in hypertensive patients with LVH. Increased QT interval and QT dispersion are electrocardiographic (ECG) measures of ventricular repolarization, and also risk markers for ventricular tachyarrhythmias. We assessed the relation of QT intervals and QT dispersion to echocardiographically determined left ventricular (LV) mass and geometry in a large population of hypertensive patients with ECG evidence of LVH. METHODS: QT intervals and QT dispersion were determined from baseline 12-lead ECGs in 577 (57% male; mean age 65 +/- 7 years) participants in the LIFE study. LV mass index (LVMI) and geometric pattern were determined by echocardiography and QT interval duration and QT dispersion were assessed in relation to gender-specific LVMI quartiles. RESULTS: In both genders, increasing LVMI was associated with longer rate-adjusted QT intervals. QT dispersion measures showed a weaker association with LVMI quartiles. Both concentric and eccentric LVH were associated with increased QT interval duration and QT dispersion. These relations remained significant after controlling for relevant clinical variables. CONCLUSIONS: In hypertensive patients with ECG evidence of LVH, increased LVMI and LVH are associated with a prolonged QT interval and increased QT dispersion. These findings suggest that an increased vulnerability to repolarization-related ventricular arrhythmias might in part explain the increased risk of sudden death in hypertensive patients with increased LV mass.

Left ventricular wall stresses and wall stress-mass-heart rate products in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint reduction in hypertension.

OBJECTIVE: Left ventricular (LV) hypertrophy on echocardiogram (ECG) strongly predicts coronary heart disease events, but the mechanisms linking increased LV mass to ischemic vascular events is uncertain. DESIGN: Variables related to myocardial oxygen demand were compared among normotensive adults and patients with mild and more severe hypertension, and among groups of moderately hypertensive patients with target organ damage in relation to gender, LV geometry and LV systolic function. SETTING: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, in which hypertensive patients with ECG LV hypertrophy (Cornell voltage-duration product, > 2440 mm x ms and/or SV1 + RV(5-6) > 38 mm) were randomized to > or = 4 years double-blinded treatment with losartan or atenolol. PATIENTS/PARTICIPANTS: A total of 964 LIFE participants enrolled in an echocardiographic substudy, and groups of 282 employed hypertensive and 366 apparently normal adults. INTERVENTIONS: None. MAIN OUTCOME MEASURES: ECG LV parameters contributing to myocardial oxygen demand (wall stresses, LV mass, heart rate and wall stress-mass-heart rate products). RESULTS: In both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall stresses, mass and stress-mass-heart rate products. LIFE men patients had slightly higher wall stresses and significantly higher triple products than women. Wall stresses were increased in patients with normal LV geometry, eccentric or concentric hypertrophy; triple products were about three and two times normal with eccentric and concentric hypertrophy, with smaller increases in other geometric groups. Patients with decreased LV fractional shortening had two times normal end-systolic stresses and three or four times normal triple products; smaller increases in stresses and triple products occurred with decreased LV midwall function. CONCLUSIONS: Hypertensive patients with ECG LV hypertrophy have increased LV wall stresses and stress-mass-heart rate products, suggesting a contribution of high myocardial oxygen demand to increased risk in such patients. Particularly high stresses and triple products were associated with echocardiographic LV hypertrophy, and subnormal LV chamber and midwall function.