Opposite effects of losartan and atenolol on natriuretic peptides in patients with hypertension and left ventricular hypertrophy: a LIFE substudy

BACKGROUND: Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin-angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP). METHODS: In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens. RESULTS: There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125-1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7-18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100-1640 pmol/l, P < 0.001) and Nt-proBNP (20.0-37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = -0.16, P < 0.001) and Nt-proBNP (r = -0.07, P = 0.08) were negatively related to change in heart rate. CONCLUSION: Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.     

Pulse pressure and effects of losartan or atenolol in patients with hypertension and left ventricular hypertrophy

In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the primary composite end point of cardiovascular death, stroke, and myocardial infarction was reduced by losartan versus atenolol in patients with hypertension and left ventricular hypertrophy. The objective of this post hoc analysis was to determine the influence of pulse pressure on outcome. Patients were divided into quartiles of baseline pulse pressure. Cox regression, including baseline Framingham risk score as a covariate, was used to compare risk in the quartiles. In the atenolol group, there were significantly higher risks in the highest versus lowest quartile for the composite end point 28% (confidence interval [CI], 2% to 62%; P=0.035), stroke 84% (CI, 32% to 157%; P<0.001), and total mortality 41% (CI, 7% to 84%; P=0.013). Risk for myocardial infarction was 44% higher (CI, -5% to 120%; P=0.089). The risks in the losartan group also increased with increasing quartile, but were lower than in the atenolol group, and differences between the highest and lowest quartiles were not significant: composite end point 12% (CI, -13% to 44%; P>0.2), stroke -5% (CI, -34% to 37%; P>0.2), myocardial infarction 30% (CI, -13% to 94%; P>0.2), and total mortality 32% (CI, -1% to 76%; P=0.062). In patients with hypertension and left ventricular hypertrophy in the LIFE study, there were significantly higher risks, adjusted for the Framingham risk score, for the primary composite end point, stroke, and total mortality in the highest versus lowest quartile of pulse pressure with atenolol-based treatment. The risks in the losartan group also increased with increasing pulse pressure quartile, but were lower than those in the atenolol group, and were not significant.     

Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential hypertension and left ventricular hypertrophy

OBJECTIVE: To compare the effects of the angiotensin II antagonist, losartan, with those of atenolol on left ventricular hypertrophy (LVH), blood pressure and neurohormone concentrations in hypertensive patients with LVH. DESIGN: A multinational, randomized, double-blind trial. SETTING: Hospital. PATIENTS: Hypertensive patients with an echocardiographically documented left ventricular mass index (LVMI) 120 g/m(2) (men) or 105 g/m(2) (women). INTERVENTIONS: Patients allocated randomly to groups received either losartan or atenolol 50 mg/day for 36 weeks, with possible titration to 100 mg/day, and addition of hydrochlorothiazide 12.5 or 25 mg/day. MAIN OUTCOME MEASURES: Changes in LVMI and sitting systolic (SBP) and diastolic (DBP) blood pressures after 36 weeks of treatment (study powered for non-inferiority hypothesis). All echocardiographic data were read in a central laboratory by staff blinded to the treatments and sequence of echocardiographic tapes. RESULTS: The estimated treatment difference between the losartan and atenolol regimens (mean change from baseline at week 36) in LVMI was -2.5 g/m(2) [95% confidence interval (CI) -7.36 to 2.37 g/m(2) ] in favor of losartan, indicating that losartan was significantly non-inferior ( 0.001, non-inferiority limit 8 g/m(2) ) and numerically superior to atenolol in reducing LVMI. The losartan-based regimen significantly reduced LVMI after 36 weeks compared with baseline (-6.56 g/m(2) , 95% CI -10.24 to -2.88 g/m(2) , P<0.001), whereas the atenolol-based regimen had no significant effect (-3.71 g/m, 95% CI -7.75 to 0.32 g/m(2) , P= NS). In a subset of 82 patients, significant changes in serum concentrations of atrial natriuretic peptide, brain natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic peptide were recorded in losartan-treated ( 0.01) but not atenolol-treated patients. Losartan and atenolol significantly decreased SBP and DBP from baseline after 6, 12, 24 and 36 weeks. The changes from baseline in DBP were greater in the atenolol group at weeks 6 and 36 [difference -2.6 mmHg ( P= 0.016) at week 36]. However, both treatment regimens achieved similar SBP/DBP values at week 36 (141.1 +/- 12.8/86.8 +/- 8.2 mmHg for losartan and 141.4 +/- 17.2/85.0 +/- 10.1 mmHg for atenolol, respectively). Overall, losartan treatment was associated with significantly fewer drug-related clinical adverse events, compared with atenolol (10 and 22%, respectively, P= 0.028). CONCLUSIONS: Both losartan- and atenolol-based regimens effectively decreased blood pressure. Losartan was non-inferior and numerically superior to atenolol in regression of LVH. The reduction in hypertrophy with losartan treatment was accompanied by reductions in circulating concentrations of cardiac natriuretic peptides. Losartan, by specifically blocking angiotensin II, may therefore have effects on the heart beyond those expected from the decrease in blood pressure alone. Losartan was better tolerated than atenolol.     

Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICARUS, a LIFE substudy

Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P<0.0001), and also during hyperinsulinaemia (P<0.0001). Plasma noradrenaline did not change significantly from placebo treatment at baseline to year 1, but increased significantly during hyperinsulinaemia both at baseline and at year 1 (P<0.0001 for both). There were no differences in plasma catecholamines or the relative changes between the two treatment arms at any stage. In a subset of 42 patients examined also at years 2 and 3, these findings were confirmed during long-term treatment. Thus, losartan had an effect on plasma catecholamines comparable to that with the beta-blocker atenolol in patients with hypertension and left ventricular hypertrophy at rest and during hyperinsulinaemia. We find it unlikely that a difference in sympathetic activity explains the outcome benefits of losartan over atenolol in the LIFE study.     

Prothrombotic factors, endothelial function and left ventricular hypertrophy in isolated systolic hypertension compared with systolic-diastolic hypertension.

BACKGROUND: Individuals with systolic-diastolic hypertension (SDH, systolic blood pressure (SBP) >160 mm Hg and diastolic blood pressure (DBP) >90 mm Hg) are at increased risk of thrombotic complications, such as stroke and heart attacks, which may be related to a hypercoagulable state. Individuals with only isolated systolic hypertension (ISH; i.e. SBP >160 mm Hg but DBP <90 mm Hg) are also at significant cardiovascular risk. We hypothesized that patients with ISH would exhibit a prothrombotic state similar to that seen in SDH. A secondary hypothesis was that individuals with ISH had similar echocardiographic parameters to those seen in SDH. METHODS: We measured indices of haemorheology, endothelial dysfunction, thrombogenesis and platelet activation in 23 individuals with ISH (mean blood pressure 193/82 mm Hg), who were compared with 51 matched patients with SDH (mean blood pressure 198/112 mm Hg) and 34 age- and sex- matched normotensive healthy control individuals (mean blood pressure 130/78 mm Hg). Echocardiographic parameters in patients with ISH were compared to those from patients with SDH. RESULTS: Mean plasma viscosity (an index of blood rheology, ANOVA, P = 0.001), von Willebrand factor (an index of endothelial damage, P = 0.013), plasminogen activator inhibitor-1 and lipoprotein (a) (both markers of thrombogenesis; Kruskal-Wallis test, both P<0.001) were all significantly raised in ISH and SDH relative to controls. Individuals with SDH also had high mean plasma fibrinogen (P = 0.018) and haematocrit (P = 0.010) levels compared with control individuals. There were no significant differences in levels of fibrin D-dimer or the platelet activation marker soluble P-selectin in the hypertensive patients (i.e. ISH and SDH) compared with control individuals. Patients with ISH had similar M-mode and Doppler echocardiographic parameters compared to patients with SDH. CONCLUSIONS: We conclude that individuals with ISH have abnormalities in plasma prothrombotic factors and markers of endothelial dysfunction, and echocardiographic parameters, broadly similar to that seen in SDH. This is consistent with the increased risk of thrombotic events (strokes and heart attacks) in patients with ISH.     

Effect of hemoglobin levels on cardiovascular outcomes in patients with isolated systolic hypertension and left ventricular hypertrophy (from the LIFE study)

The optimal hemoglobin level in patients with hypertension or heart failure is not yet defined. The aim of the present investigation was to examine the relation of hemoglobin with cardiovascular outcomes in high-risk patients with isolated systolic hypertension (ISH) and left ventricular hypertrophy (LVH). In 1,326 patients with ISH in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, hemoglobin and cardiovascular outcomes were examined using Cox proportional hazard models. Baseline hemoglobin was negatively related to rate of cardiovascular death (hazard ratio 0.81 per 1 g/dl, 95% confidence interval [CI] 0.67 to 0.98, p = 0.032) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. Hemoglobin decreased slightly during the study and the decrease was more pronounced in the losartan group (13.9 +/- 1.3 to 13.6 +/- 1.4 g/dl) than in the atenolol group (13.9 +/- 1.2 to 13.8 +/- 1.4 g/dl). Hemoglobin as a time-varying covariate was negatively associated with rate of cardiovascular death (hazard ratio 0.75, 95% CI 0.63 to 0.90, p <0.001) and stroke (hazard ratio 0.84, 95% CI 0.72 to 0.99, p = 0.040) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. In conclusion, in this high-risk population with ISH and LVH, lower hemoglobin at baseline was associated with higher probability of cardiovascular death, and decrease in hemoglobin over time was associated with higher probability of cardiovascular death or stroke; this effect was attenuated by treatment with losartan.     

氯沙坦对老年高血压病患者心室肥大和QTd的影响

目的　评价氯沙坦对老年原发性高血压病患者左心室肥大及 QT离散度 (QTd)的影响。方法　依据是否伴有左心室肥大 ,将 5 7例轻、中度高血压病患者分为两组 ,分别给予氯沙坦 5 0 mg/d,或氯沙坦 5 0 m g/d加双氢克尿噻12 .5 mg/d治疗 ,共 16～ 18周 ,比较两组治疗前后左心室大小 ,及 QTd改变 ,并分析 L VMI与 QTd的相关性。结果　治疗后高血压伴左心室肥大组 L VDd,IVST,PWT,L VMI比治疗前下降 (P<0 .0 5或 P<0 .0 1)。高血压伴左心室肥大组 QTd比不伴左心室肥大组大 (P<0 .0 1) ,治疗后则明显减小 (P<0 .0 1)。高血压伴左心室肥大组 L VMI与 QTd有较好的相关性。结论　氯沙坦或氯沙坦加双氢克尿噻能逆转老年高血压病患者的左心室肥大 ,并使 QTd相应减小。     

Impact of age on left ventricular hypertrophy regression during antihypertensive treatment with losartan or atenolol (the LIFE study)

To assess the influence of age on changes in left ventricular (LV) mass and geometry during antihypertensive treatment, we related age to clinical and echocardiographic findings before and after 4 years of antihypertensive treatment in a subset of 560 hypertensive patients without known concurrent disease in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which randomized patients to blinded losartan- or atenolol-based treatment. Patients >/=65 years (older group) included more women and patients with isolated systolic hypertension or albuminuria (all P<0.05). Compared to patients <65 years, older patients had higher pulse pressure, LV mass, and prevalence of concentric hypertrophy at baseline (78 vs 69 mmHg, 234 vs 224 g, and 28 vs 16%, respectively, all P<0.01), while the mean blood pressure did not differ. Over 4 years, reductions in LV mass and the mean blood pressure were similar in both groups, but older patients more often had residual hypertrophy (31 vs 15%, P<0.001) with a preponderance of eccentric geometry. In multivariate analysis of 4-year change in LV mass controlling for baseline mass, larger hypertrophy reduction was associated with losartan treatment, while age, gender, body mass index, and 4-year change in pulse pressure and albuminuria did not enter (Multiple R (2)=0.40, P<0.001). Thus, in up-to-80-year-old hypertensive patients with left ventricular hypertrophy, age did not significantly attenuate hypertrophy reduction during antihypertensive treatment, although residual hypertrophy was more prevalent in older patients as a consequence of higher initial LV mass.     

Similar effects of isolated systolic and combined hypertension on left ventricular geometry and function: the LIFE study

Echocardiograms of 143 patients with isolated systolic hypertension were compared to 808 patients with combined (systolic and diastolic) hypertension. All patients met electrocardiographic criteria for left ventricular hypertrophy and were evaluated off medication. Patients with isolated systolic hypertension were older, shorter, weighed less, and were mostly women, but body mass index (BMI) was similar in both groups. Systolic blood pressure (SBP) was 172 mm Hg in isolated systolic hypertension, 174 mm Hg in combined (P = not significant). Diastolic blood pressure was 83 and 101 mm Hg, respectively (P < .001). Despite having mean arterial pressure 12 mm Hg lower than patients with combined hypertension, the group with isolated systolic hypertension had equally severe abnormalities of left ventricular mass, left ventricular geometric patterns, and measures of systolic and diastolic function. Peripheral resistance was lower and pulse pressure/stroke volume ratio (arterial stiffness index) was higher and the isovolumic relaxation time shorter in isolated systolic hypertension. Multiple regression analyses identified age, height, BMI, stress-corrected mid wall shortening, stroke volume, male gender, and systolic or mean blood pressure (but not isolated systolic hypertension) as independent correlates of left ventricular mass. Relative wall thickness was independently associated with isolated systolic hypertension (P = .001) in addition to mean pressure and other covariates. The present results add support to the concept that systolic blood pressure (SBP) is a stronger determinant than diastolic pressure of cardiac target organ damage in hypertension.     

单纯收缩期高血压患者血管内皮功能与左心室肥厚的关系

目的探讨单纯收缩期高血压患者血流介导的血管舒张功能(FMD)与左心室肥厚(LVH)的关系。方法选择单纯收缩期高血压患者200例,根据左心室质量指数分为:LVH组73例和非LVH组127例,同期选择年龄匹配的健康体检者50例作为对照组,采用超声技术测定FMD,ELISA法检测外周血清晚期糖基化终末产物(AGEs)和内皮素1,Griess法测定外周血NO含量。结果与非LVH组和对照组比较,LVH组FMD明显降低,AGEs和内皮素1均明显升高(P0.01)。左心室质量指数与AGEs和内皮素1呈显著正相关(r=0.639,P=0.015;r=0.428,P=0.036),与FMD和NO呈显著负相关(r=-0.718,P=0.003;r=-0.337,P=0.041);FMD和AGEs为LVH的独立危险因素(P=0.027,P=0.035);随着FMD降低、AGEs增加,LVH发病的危险性明显增加。结论血管内皮功能减退和大动脉硬化是单纯收缩期高血压患者LVH的独立危险因素。     

老年人收缩期高血压左室肥厚与心律失常关系的探讨

目的探讨老年人收缩期高血压（ＯＩＳＨ）左室肥厚（ＬＶＨ）与心律失常的发生及其关系。方法对９６例ＯＩＳＨ患者进行超声心动图和Ｈｏｌｔｅｒ检查,比较有ＬＶＨ及无ＬＶＨ两组各类心律失常的发生情况。结果９６例ＯＩＳＨ患者并发ＬＶＨ者６２例（６４．６％）;ＬＶＨ组复杂性房性与室性心律失常例数分别为５５例（８８．７％）与４８例（７７．４％）,其构成比显著高于无ＬＶＨ组的３５．３％（１２例）与３２．４％（１１例）（均为Ｐ＜０．０１）。结论ＯＩＳＨ患者ＬＶＨ与复杂性房性和室性心律失常密切相关。     

Losartan benefits over atenolol in non-smoking hypertensive patients with left ventricular hypertrophy: the LIFE study

We studied the impact of smoking in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios in 4656 never-smokers, and 3033 previous and 1499 current smokers, adjusting for gender, age, alcohol intake, exercise and race. Composite endpoint rate was higher in previous (28/1000 years), as well as current (39/1000 years) smokers than in never-smokers (21/1000 years). Composite (hazard ratio 0.78, 95% CI 0.65-0.94, p < 0.01) and stroke (hazard ratio 0.61, 95% CI 0.47-0.80], p < 0.001) risks were lower with losartan than atenolol in never-smokers, but not significantly in previous smokers. Drug regimens did not differ in current smokers (composite hazard ratio 0.99, stroke hazard ratio 0.94). Smoking-treatment interactions were non-significant, but a borderline significant trend (p = 0.05) suggested decreasing benefit of losartan vs atenolol for stroke prevention from never- to previous to current smoking status. Smoking increased cardiovascular risk markedly in the LIFE study. The benefit of losartan vs atenolol is consistent with the overall conclusion of the LIFE study, although the treatment effect appeared largest in non-smokers.     

氯沙坦与福辛普利逆转原发性高血压左心室肥厚的对比研究

目的 :对比研究应用氯沙坦和福辛普利逆转原发性高血压 (EH)伴左心室肥厚 (LVH)的作用。方法 :将 12 0例EHLVH患者随机分为氯沙坦组 (n =6 0 )和福辛普利组 (n =6 0 ) ,于服药前及服药 6个月后分别测定血压、室间隔厚度 (IVST)、左心室后壁厚度 (PWT)、左心室舒张末期直径 (LVDd)、左心室重量指数 (LVMI)、左心室射血分数 (LVEF)、心排血量 (CO)和A/E峰值。结果 :两组患者经治疗后血压、IVST、PWT、LVDd、LV MI、A/E峰值均显著降低 (均P <0 .0 1) ,而LVEF、CO无显著变化 (P >0 .0 5 )。结论 :氯沙坦与福辛普利均能逆转LVH ,明显改善左心室舒张功能     

Left atrial systolic force in hypertensive patients with left ventricular hypertrophy: the LIFE study

In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial systolic force and left ventricular geometry and function have not been investigated in high-risk hypertrophic hypertensive patients. Participants in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy without prevalent cardiovascular disease or atrial fibrillation (n = 567) underwent standard Doppler echocardiography. Left atrial systolic force was obtained from the mitral orifice area and Doppler mitral peak A velocity. Patients were divided into groups with normal or increased left atrial systolic force (>14.33 kdyn). Left atrial systolic force was high in 297 patients (52.3%), who were older and had higher body mass index and heart rate (all P < 0.01) but similar systolic and diastolic blood pressure, in comparison with patients with normal left atrial systolic force. After controlling for confounders, increased left atrial systolic force was associated with larger left ventricular diameter and higher left ventricular mass index (both P < 0.01). Prevalence of left ventricular hypertrophy was greater (84 vs. 64%; P < 0.001). Participants with increased left atrial systolic force exhibited normal ejection fraction; higher stroke volume, cardiac output, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P < 0.01). Enhanced left atrial systolic force identifies hypertensive patients with greater left ventricular mass and prevalence of left ventricular hypertrophy, but normal left ventricular chamber systolic function with increased transmitral flow gradient occurring during early filling, consistent with increased preload.     

The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension. Losartan ISH Investigators Group

OBJECTIVE: To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the beta-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment. METHODS: A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP > or = 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. RESULTS: Similar significant reductions in SiSBPs (mean +/- SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 +/- 10.3 and 173.5 +/- 10.7 mmHg at baseline to 149.0 +/- 15.5 and 148.2 +/- 15.3 mmHg after 16 weeks of losartan or atenolol treatment respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029). CONCLUSION: It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.     

Gender differences in systolic left ventricular function in hypertensive patients with electrocardiographic left ventricular hypertrophy (the LIFE study)

Echocardiography was performed in 944 untreated hypertensive patients (391 women and 553 men, mean age 66 years) who had electrocardiographic left ventricular (LV) hypertrophy at baseline in the Losartan Intervention For End point reduction in hypertension (LIFE) study to evaluate gender-associated differences in systolic LV function. Women had significantly lower diastolic blood pressure (175/97 vs 173/99 mm Hg) and body surface area and a higher body mass index (all p < 0.01). Women also had higher LV ejection fraction (EF), endocardial and midwall fractional shortening (63% vs 60%, 35% and 33%, and 16% vs 15%, respectively, all p < 0.01), higher stress-corrected midwall fractional shortening (98% vs 96%, p < 0.05), and lower circumferential end-systolic wall stress (178 vs 187 kdynes/cm(2), p < 0.01). There was no difference in age or LV mass indexed for height(2.7), but relative wall thickness was higher in women (0.42 vs 0.41, p < 0.05). In multiple regression analyses: (1) EF and endocardial fractional shortening were 2% to 3% higher in women than men, independent of the effects of LV stress, body mass index, and height (multiple r = 0.77 and 0.75, respectively, gender p < 0.02 in both models); (2) midwall fractional shortening was 0.5% higher in women, independent of the effects of age, body mass index, circumferential end-systolic stress, and absence of diabetes (multiple r = 0.36, p = 0.014 for gender); and (3) stress-corrected LV midwall fractional shortening was 2% higher (p = 0.004) in women, independent of the effects of age, height, heart rate, body mass index, and diabetes (multiple r = 0.33). Thus, female gender is an independent predictor of higher systolic LV function in hypertensive patients with electrocardiographic LV hypertrophy.