Association of left bundle branch block with cardiovascular morbidity and mortality in hypertensive patients with left ventricle hypertrophy: the life study

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POSTERS: Clinical Trials

whites and 44⫾1 years for blacks) and the other in 93 white hypertensives (age: 50⫾1 years) and 39 white normotensives (age: 28⫾2 years), where salt intake was reduced from 350 to 10-20 mmol/day, for 5 days. Gradual increase in salt intake: Six normotensive subjects (age range: 19 –21 years) were placed on a low salt diet of 10 mmol/day throughout the study. After a 4-day equilibration period, salt intake was progressively increased by 50 mmol/day until salt intake reached 250 mmol/day. Longer-term modest salt reduction: 118 hypertensive individuals (age: 56⫾1 years) were studied in randomised double blind crossover studies of one month of usual salt intake and one month of modestly reduced salt intake. Results: Acute and large salt reduction: There was a decrease in plasma sodium of approximately 3 mmol/L (P⬍0.001) in both white and black hypertensives as well as in white normotensives. Gradual increase in salt intake: Plasma sodium was increased from 139⫾0.7 to 142⫾1.1 mmol/L (P⬍0.001 by Repeated Measures ANOVA). Longer-term modest salt reduction: Plasma sodium was decreased by 0.4⫾0.2 mmol/L (P⬍0.05) with a reduction in urinary sodium of 78⫾6 mmol/24h. The decrease in plasma sodium was associated with the fall in systolic BP (r⫽0.18, P⬍0.05). Conclusion: When salt intake is increased or decreased, there is a reciprocal change in plasma sodium. Changes in plasma sodium are the immediate drive to the changes in extracellular volume by altering thirst and the movement of fluid between intracellular and extracellular fluid compartment. However, there is now increasing evidence that these small changes in plasma sodium may directly affect hypothalamus, the local renin-angiotensin system, and both the heart and vasculature, all of which may play a role in changing BP independent of and additive to that occurs with the tendency for the changes in extracellular volume. Key Words: Salt Intake, Plasma Sodium,

P-405 IN BRITISH ASIAN HYPERTENSIVE PATIENTS, DOXAZOSIN PROVIDES GREATER IMPROVEMENT IN GLYCEMIC CONTROL AND LIPID PROFILE THAN BENDROFLUAZIDE F.D. Richard Hobbs. Primary Care and General Practice, University of Birmingham, Birmingham, Birmingham, United Kingdom. British Asians from the Indian subcontinent have an increased risk of mortality due to coronary heart disease associated with metabolic syndrome compared with the general population. This study evaluated the metabolic effects of the ␣1-adrenoceptor blocker doxazosin (DOX) and the diuretic bendrofluazide (BFZ) in British Asians with hypertension. Secondary objectives included the antihypertensive efficacy and tolerability of DOX and BFZ. Following a 2-Wk placebo run-in, DOX (1, 2, 4, or 8 mg; n⫽78) or BFZ (2.5 mg, n⫽82) was administered for 34 Wk in a randomized double-blind parallel group study of patients of British Asian origin with hypertension. DOX was titrated from 1 to 8 mg per day at Wk 2, 4, or 6, depending on blood pressure (BP) response. Amlodipine (5 mg) was added to the regimen after Wk 8 if diastolic BP had not decreased by 5 mmHg from the previous visit or was ⱖ90 mmHg. The primary efficacy variables were changes in mean serum glucose and total cholesterol between baseline and Wk 21. DOX reduced glucose, insulin, total cholesterol, LDL cholesterol, and triglycerides and increased mean HDL cholesterol. A significant treatment difference in favor of DOX compared with BFZ was observed for glucose at Wk 21 (– 0.14 mmol/L; 95% CI: – 0.26 to – 0.01; P⫽0.029) and Wk 34 (⫺0.17 mmol/L; 95% CI: ⫺0.3 to ⫺0.03; P⫽0.015), fasting insulin at Wk 34 (–20.8 pmol/L; 95% CI: ⫺31.3 to ⫺10.3; P⬍0.001), total cholesterol at Wk 21 (– 0.22 mmol/L; 95% CI: ⫺0.43 to 0.00; P⫽0.048), and triglycerides at Wk 21 (⫺0.13 mmol/L; 95% CI: ⫺0.27 to 0.00; P⫽0.047) and Wk 34 (⫺0.20 mmol/L; 95% CI: ⫺0.35 to ⫺0.05; P⫽0.009). Amlodipine was administered to 15.4% of DOX- and 22.0% of BFZ-treated patients. Both drugs reduced BP vs baseline with no significant differences between groups. A similar number of adverse events were seen in both groups. In conclu-

AJH–May 2004 –VOL. 17, NO. 5, PART 2

sion, DOX was more effective than BFZ in lowering glucose concentrations and improving lipid profiles in hypertensive British Asians. DOX has beneficial effects on components of insulin resistance as well as BP in this ethnic population. Both agents were well tolerated. Key Words: Adrenoceptor Antagonist, Hypertension, Glycemic Control

P-406 ASSOCIATION OF LEFT BUNDLE BRANCH BLOCK WITH CARDIOVASCULAR MORBIDITY AND MORTALITY IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICLE HYPERTROPHY: THE LIFE STUDY Zhibin Li, Richard B. Devereux, Sverre E. Kjeldsen, Stevo Julius, Kristian Wachtell, Hans Ibsen, Markku S Nieminen, Sverker Jern, Peter M Okin, Bjorn Dahlof. Department of Medicine, Division of Cardiology, Weill Medical College of Cornell University, New York, NY; Department of Medicine, Ullevaal University Hospital, Oslo, Norway; Department of Medicine, University of Michigan Medical Center, Ann Arbor, MI; Department of Medicine, Copenhagen County University Hospital, Copenhagen, Glostrup, Denmark; Department of Medicine, Copenhagen University Hospital Glostrup, Copenhagen, Glostrup, Denmark; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Department of Medicine, Sahlgrenska University Hospital, Ostra, Goteborg, Sweden; Department of Medicine, Sahlgrenska University Hospital, Ostra, Gothenburg, Sweden. To study cardiovascular morbidity and mortality in hypertensive patients with and without left bundle branch block (LBBB) in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Hypertensive patients with left ventricle hypertrophy by Cornell voltage-duration product or Sokolow-Lyon voltage criteria on a screening electrocardiogram (ECG) were randomized to treatment with losartan or atenolol and followed a mean of 4.8 years. ECGs were read at a central laboratory; Minnesota code 7.1 identified LBBB. The composite endpoint of the LIFE study (cardiovascular death and non-fatal or fatal stroke or myocardial infarction) and its components were adjudicated by an expert endpoint committee. Cox regression models, using the Framingham risk score and randomized treatment assignment as covariates, were used to assess the association of LBBB with endpoints. The LIFE study baseline ECG showed LBBB in 564 patients (338 women; mean age 66.8⫾7.0 years) and no LBBB in 8566 patients (4593 women; mean age 68.6⫾6.6 years). There was no significant difference between patients with and without LBBB in the proportion of patients who suffered the composite endpoint (12.4 vs. 11.9%), myocardial infarction (3.0 vs. 4.3%) or stroke (4.4 vs. 6.0%), but patients with LBBB were more likely to suffer cardiovascular death (8.3 vs. 4.5%, p⬍0.001). In Cox regression analysis adjusting for the Framingham risk score and randomized treatment assignment, LBBB was independently associated with a 1.84-fold higher rate of cardiovascular mortality (95% CI 1.34 – 2.53, p⬍0.001). LBBB was also associated with significantly higher all-cause mortality (hazard ratio 1.34 [95% CI 1.01–1.78], p⫽0.041) independent of randomized treatment assignment and Framingham risk score. Among hypertensive patients with ECG defined left ventricle hypertrophy , the presence of LBBB identifies significantly increased risk of cardiovascular and all-cause mortality. Key Words: Left Bundle Branch Block, Hypertensive, Left Ventricle Hypertrophy