In-treatment reduced left atrial diameter during antihypertensive treatment is associated with reduced new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophy: The LIFE Study.

OBJECTIVE: It is unclear whether improvement of left atrial (LA) and ventricular (LV) structure results in reduction in new-onset atrial fibrillation (AF). The aim of the present study was to examine whether changes in-treatment LA diameter were related to changes in risk of new-onset AF. METHODS: We followed 939 hypertensive patients with electrocardiographic LV hypertrophy randomized to atenolol or losartan-based regimens in the LIFE Study for a mean of 4.8 years with echocardiograms at enrolment and annually during treatment. RESULTS: New-onset AF occurred in 46 patients (10.2/1000 patient-years of follow-up). At baseline, patients with new-onset AF were older, had higher systolic blood pressure and heart rate as well as higher prevalence of LA dilatation, but had similar prevalences of LV hypertrophy and mitral or aortic valve disease. In univariate Cox analysis baseline LA diameter (HR=4.67 per cm increase [95% CI 2.86-7.65], p<0.001) and LV mass index (HR=1.11 per 10 g/m(2) increase [95% CI 1.02-1.22], p<0.05) both predicted new-onset AF. In multivariate analysis, increased baseline LA diameter increased the risk of new-onset AF (HR=5.16 per cm [95% CI 2.85-9.35], p<0.001) whereas reduction of in-treatment LA diameter reduced the risk (HR=0.21 per cm lower LA diameter during treatment [95% CI 0.14-0.32], p<0.001) with adjustment for in-treatment LV mass in-treatment systolic blood pressure, age and Framingham risk score. CONCLUSION: LA diameter at baseline and during antihypertensive treatment were equally strong predictors of new-onset AF independent of the level of arterial pressure, LV mass and other covariates. Prevention of AF during antihypertensive treatment may be improved by antihypertensive therapy that reduces LA size in addition to controlling blood pressure.

Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study.

OBJECTIVES: We assessed the impact of antihypertensive treatment in hypertensive patients with electrocardiographic (ECG) left ventricular (LV) hypertrophy and a history of atrial fibrillation (AF). BACKGROUND: Optimal treatment of hypertensive patients with AF to reduce the risk of cardiovascular morbidity and mortality remains unclear. METHODS: As part of the Losartan Intervention For End point reduction in hypertension (LIFE) study, 342 hypertensive patients with AF and LV hypertrophy were assigned to losartan- or atenolol-based therapy for 1,471 patient-years of follow-up. RESULTS: The primary composite end point (cardiovascular mortality, stroke, and myocardial infarction) occurred in 36 patients in the losartan group versus 67 in the atenolol group (hazard ratio [HR] = 0.58, 95% confidence interval [CI] 0.39 to 0.88, p = 0.009). Cardiovascular deaths occurred in 20 versus 38 patients in the losartan and atenolol groups, respectively (HR = 0.58, 95% CI 0.33 to 0.99, p = 0.048). Stroke occurred in 18 versus 38 patients (HR = 0.55, 95% CI 0.31 to 0.97, p = 0.039), and myocardial infarction in 11 versus 8 patients (p = NS). Losartan-based treatment led to trends toward lower all-cause mortality (30 vs. 49, HR = 0.67, 95% CI 0.42 to 1.06, p = 0.090) and fewer pacemaker implantations (5 vs. 15, p = 0.065), whereas hospitalization for heart failure took place in 15 versus 26 patients and sudden cardiac death in 9 versus 17, respectively (both p = NS). The benefit of losartan was greater in patients with AF than those with sinus rhythm for the primary composite end point (p = 0.019) and cardiovascular mortality (p = 0.039). CONCLUSIONS: Losartan is more effective than atenolol-based therapy in reducing the risk of the primary composite end point of cardiovascular morbidity and mortality as well as stroke and cardiovascular death in hypertensive patients with ECG LV hypertrophy and AF.

Change in diastolic left ventricular filling after one year of antihypertensive treatment: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study.

BACKGROUND: It is well established that hypertensive patients with left ventricular (LV) hypertrophy have impaired diastolic filling. However, the impact of antihypertensive treatment and LV mass reduction on LV diastolic filling remains unclear. METHODS AND RESULTS: Echocardiograms were recorded in 728 hypertensive patients with ECG-verified LV hypertrophy (Cornell voltage-duration or Sokolow-Lyon) at baseline and after 1 year of blinded treatment with either losartan or atenolol-based regimen. Systolic and diastolic blood pressures (BP) were reduced on average 23/11 mm Hg; isovolumic relaxation time and E/A ratio became more normal, and LV inflow deceleration time prolonged (all P<0.001). Directionally opposite changes in isovolumic relaxation time (IVRT) and deceleration time indicate improvement in active LV relaxation and passive chamber stiffness during early diastole. Prevalences of normal LV filling increased, abnormal relaxation and pseudonormalization decreased, and restrictive filling pattern remained unchanged (P<0.05). Patients with reduction in LV mass had smaller left atrial diameter, shortened IVRT, increased E/A ratio, and prolonged LV inflow deceleration time (all P<0.001). Patients without LV mass reduction had no change in diastolic filling parameters (P=NS). IVRT shortening was independently associated with reduction in LV mass. Increase in E/A ratio was independently associated with reduction in diastolic BP, and increase in the deceleration time was independently associated with reduced end-systolic relative wall thickness. CONCLUSIONS: Antihypertensive therapy resulting in LV mass or relative wall thickness regression is associated with significant improvement of diastolic filling parameters related to active relaxation and passive chamber stiffness compared with patients without regression, independent of BP reduction; however, abnormalities of diastolic LV filling remain common.

Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial.

BACKGROUND: An echocardiographic substudy of the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial was designed to test the ability of losartan to reduce left ventricular (LV) mass more than atenolol. METHODS AND RESULTS: A total of 960 patients with essential hypertension and LV hypertrophy (LVH) on screening ECG were enrolled at centers in 7 countries and studied by echocardiography at baseline and after 1, 2, 3, 4, and 5 years' randomized therapy. Clinical examination and blinded readings of echocardiograms in 457 losartan-treated and 459 atenolol-treated participants with > or =1 follow-up measurement of LV mass index (LVMI) were used in an intention-to-treat analysis. Losartan-based therapy induced greater reduction in LVMI from baseline to the last available study than atenolol with adjustment for baseline LVMI and blood pressure and in-treatment pressure (-21.7+/-21.8 versus -17.7+/-19.6 g/m2; P=0.021). Greater LVMI reduction with losartan was observed in women and men, participants >65 or <65 years of age, and with mild or more severe baseline hypertrophy. The difference between treatment arms in LVH regression was due mainly to reduced concentricity of LV geometry in both groups and lesser increase in LV internal diameter in losartan-treated patients. CONCLUSIONS: Antihypertensive treatment with losartan, plus hydrochlorothiazide and other medications when needed for pressure control, resulted in greater LVH regression in patients with ECG LVH than conventional atenolol-based treatment. Thus, angiotensin receptor antagonism by losartan has superior efficacy for reversing LVH, a cardinal manifestation of hypertensive target organ damage.

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.

Relation of impaired left ventricular filling to systolic midwall mechanics in hypertensive patients with normal left ventricular systolic chamber function: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study.

BACKGROUND: Patients with hypertensive left ventricular (LV) hypertrophy commonly have diastolic dysfunction with preserved LV ejection fraction. LV systolic midwall shortening (MWS) may be impaired in hypertensive patients with normal LV ejection fraction. However, it is unclear whether impaired LV filling is related to depressed systolic midwall mechanics. METHODS: Echocardiographic measures of LV diastolic filling and systolic performance were compared in 632 unmedicated patients with stage II or III hypertension and LV hypertrophy determined by electrocardiogram, with LV ejection fraction >55% and <2+ mitral regurgitation. RESULTS: Stress-corrected LV MWS, an index of myocardial contractility, was lower in patients with abnormal as opposed to normal LV filling patterns (98% +/- 12% vs 102% +/- 10%, P <.001) and in patients with prolonged as opposed to normal isovolumic relaxation time (IVRT) (98% +/- 13% vs 101% +/- 12%, P =.014). Stress-corrected MWS was <85% of predicted levels in more patients with abnormal LV filling patterns (11.8% vs 6.3%) or with long IVRT (> or =105 msec) (34% vs 21%, both P <.05). In regression analyses, lower stress-corrected MWS and higher LV mass were independent correlates of longer IVRT, while lower stress-corrected MWS was the only independent correlate of prolonged mitral valve deceleration time (P =.017). Higher LV mass had strong, statistically independent relationships to longer IVRT (by 0.3 g/msec) and decreased stress-corrected MWS (by 0.5 g/%; both P <.0001), independent of body size and age. CONCLUSION: In patients with moderate hypertension and target organ damage who have normal LV ejection fraction, impaired early diastolic LV relaxation (abnormal E/A ratio, prolonged IVRT and deceleration time) is associated with impaired LV systolic midwall mechanics independent of higher LV mass.

Is cardiovascular remodeling in patients with essential hypertension related to more than high blood pressure? A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.

BACKGROUND: Blocking the renin-aldosterone-angiotensin II system has been hypothesized to induce blood pressure-dependent as well as blood pressure-independent regression of cardiovascular hypertrophy. However, the relative influence of elevated blood pressure (BP) and various neurohormonal factors on cardiovascular remodeling in hypertension is unclear. METHODS: In 43 untreated patients with hypertension with electrocardiographic left ventricular hypertrophy, we measured relative wall thickness and left ventricular mass index by echocardiography and by magnetic resonance imaging (n = 32), intima-media cross-sectional area, and distensibility of the common carotid arteries by ultrasound, media/lumen ratio of isolated subcutaneous resistance arteries by myography, and median 24-hour systolic BP (n = 40), serum insulin, and plasma levels of epinephrine, norepinephrine, renin, angiotensin II, aldosterone, and endothelin. RESULTS: In multiple regression analyses, left ventricular mass index by echocardiography (R2 = 0.14, P <.05) and by magnetic resonance imaging (R2 = 0.32, P =.001) were associated with 24-hour systolic BP, whereas relative wall thickness was associated with plasma epinephrine (R2 = 0.12, P <.05) and aldosterone (R2 = 0.10, P <.05). Intima-media cross-sectional area/height was associated with 24-hour systolic BP (beta = 0.40) and plasma epinephrine (beta = 0.43) (adjusted R2 = 0.32, P <.001), whereas carotid distensibility was associated with 24-hour systolic BP (beta = 0.40) and plasma angiotensin II (beta = -0.41) (adjusted R2 = 0.30, P <.001). Media/lumen ratio in subcutaneous resistance arteries was associated with plasma epinephrine (R2 = 0.22, P <.01). CONCLUSION: Apart from being associated with a high BP burden, cardiovascular remodeling was associated with high levels of circulating epinephrine, aldosterone, as well as angiotensin II, suggesting a beneficial effect above and beyond the effect of BP reduction when using antihypertensive agents blocking the receptors of these neurohormonal factors.

Change of left ventricular geometric pattern after 1 year of antihypertensive treatment: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

BACKGROUND: Patients with hypertension have different types of left ventricular (LV) geometry, but the impact of blood pressure (BP) reduction on LV geometry change during antihypertensive treatment remains unclear. METHODS: Two-dimensional and M-mode echocardiograms were recorded at baseline in 853 unmedicated patients with stage II to III hypertension and LV hypertrophy determined by electrocardiography (Cornell voltage duration > or =2440 mV x ms or modified Sokolow-Lyon criteria: SV1 + RV5/RV6 >38 mV) after 14 days of placebo treatment. Follow-up echocardiography was done after 1 year of blinded treatment with either losartan or atenolol, in some cases supplemented with thiazide and calcium antagonist to reach target a BP of 140/90 mm Hg. RESULTS: Baseline systolic/diastolic BP were reduced from 174 +/- 20/95 +/- 11 to 151 +/- 19/84 +/- 11 mm Hg. LV mass was reduced from 234 +/- 56 to 207 +/- 51 g and relative wall thickness from 0.41 +/- 0.07 to 0.38 +/- 0.06 (all P <.001). Prevalence of concentric LV hypertrophy decreased from 24% to 6%, eccentric LV hypertrophy from 46% to 37%, and concentric LV remodeling from 10% to 6%; normal geometry increased from 20% to 51%. A shift toward lower LV mass and relative wall thickness was found, as approximately 73% of those with concentric LV remodeling at baseline shifted to normal geometric pattern, whereas only 7% of those with normal pattern at baseline shifted to concentric LV remodeling. Of patients with concentric LV hypertrophy at baseline, 34% shifted to eccentric LV hypertrophy, whereas only 3% with eccentric LV hypertrophy at baseline had concentric LV hypertrophy. Furthermore, multiple regression analysis showed that Doppler stroke volume reduction was a significant correlate of LV mass reduction (beta = 0.108, P <.001) independent of BP, heart rate change, and assigned drug treatment. CONCLUSIONS: Antihypertensive treatment reduces LV mass and decreases the prevalence of LV hypertrophy and concentric LV remodeling. Additional control of Doppler stroke volume potentiates the effect of BP reduction on LV mass regression independent of the BP reduction per se.

N-terminal pro-brain natriuretic peptide predicts cardiovascular events in patients with hypertension and left ventricular hypertrophy: a LIFE study.

BACKGROUND: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and N-terminal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in the general population. We investigated whether high Nt-proBNP or Nt-proANP could also predict the composite endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction in patients with hypertension and left ventricular (LV) hypertrophy. METHODS: After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 183 hypertensive participants in the LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP and Nt-proANP were measured by immunoassay at baseline. The patients were followed for 60 +/- 5 months. RESULTS: Using Cox regression analysis, the 25 CEP were predicted by ln(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01) as well as ln(Nt-proANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the median value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6 versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with higher incidence of CEP in the 123 patients without history of diabetes or cardiovascular disease (14.8 versus 4.3%, P < 0.05), but the association was insignificant in the 60 patients with a history of diabetes or cardiovascular disease (26.3 versus 18.2%, NS). Nt-proANP showed the same tendency. CONCLUSION: Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertension and LV hypertrophy, especially in patients without diabetes or clinically overt cardiovascular disease.

Effect of losartan versus atenolol on aortic valve sclerosis (a LIFE substudy).

Neither losartan- nor atenolol-based antihypertensive regimens could prevent the progression of aortic valve (AV) sclerosis in elderly, high-risk hypertensive patients, and the regression of AV sclerosis did not translate into reduced cardiovascular risk.

Vasodilatory capacity and vascular structure in long-standing hypertension: a LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.

BACKGROUND: Flow-mediated dilatation (FMD), which is considered a measure of endothelial function, has been found impaired in hypertension. However, it is unclear whether this impairment is explained solely by endothelial dysfunction, or whether it is associated with structural vascular changes and reduced vasodilatory capacity. METHODS: In 42 unmedicated patients with hypertension and electrocardiographic left ventricular hypertrophy, we measured the following: 24-h ambulatory blood pressure (BP), minimal forearm vascular resistance (MFVR) by plethysmography, intima-media cross-sectional area of the common carotid arteries (IMA), FMD, and nitroglycerin-induced dilatation (NID) in the brachial artery by ultrasound. RESULTS: We found that FMD was correlated positively with NID (r = 0.38, P < .05). However, FMD as well as NID correlated negatively to 24-h systolic BP (r = -0.41, P = .01 and r = -0.52, P = .001), IMA/height (r = -0.41, P < .01 and r = -0.53, P < .001) and MFVR(men) (r = -0.44, P < .05 and r = -0.42, P < .05). CONCLUSIONS: Low FMD as well as low NID were related in parallel to high systolic BP and to the severity of vascular changes in different vascular beds, suggesting that elevated BP load in hypertension induces parallel abnormalities in conduit artery structure and overall vasodilatory capacity. Therefore, the decrease in FMD observed in severe hypertension may be caused by endothelial dysfunction as well as by structural vascular changes, suggesting difficulties in interpreting FMD solely as a measure of endothelial dysfunction in hypertensive patients with left ventricular hypertrophy.

Prognostic significance of left ventricular mass change during treatment of hypertension.

CONTEXT: Increased baseline left ventricular (LV) mass predicts cardiovascular (CV) complications of hypertension, but the relation between lower LV mass and outcome during treatment for hypertension is uncertain. OBJECTIVE: To determine whether reduction of LV mass during antihypertensive treatment modifies risk of major CV events independent of blood pressure change. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort substudy of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) randomized clinical trial, conducted from 1995 to 2001. A total of 941 prospectively identified patients aged 55 to 80 years with essential hypertension and electrocardiographic LV hypertrophy had LV mass measured by echocardiography at enrollment in the LIFE trial and thereafter were followed up annually for a mean (SD) of 4.8 (1.0) years for CV events. MAIN OUTCOME MEASURES: Composite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke. RESULTS: The composite end point occurred in 104 patients (11%). The multivariable Cox regression model showed a strong association between lower in-treatment LV mass index and reduced rate of the composite CV end point (hazard ratio [HR], 0.78 per 1-SD (25.3) decrease in LV mass index; 95% confidence interval [CI], 0.65-0.94; P = .009) over and above that predicted by reduction in blood pressure. There were parallel associations between lower in-treatment LV mass index and lower CV mortality (HR, 0.62; 95% CI, 0.47-0.82; P = .001), stroke (HR, 0.76; 95% CI, 0.60-0.96; P = .02), myocardial infarction (HR, 0.85; 95% CI, 0.62-1.17, P = .33), and all-cause mortality (HR, 0.72; 95% CI, 0.59-0.88, P = .002), independent of systolic blood pressure and assigned treatment. Results were confirmed in analyses adjusting for additional CV risk factors, electrocardiographic changes, or when only considering events after the first year of study treatment. CONCLUSION: In patients with essential hypertension and baseline electrocardiographic LV hypertrophy, lower LV mass during antihypertensive treatment is associated with lower rates of clinical end points, additional to effects of blood pressure lowering and treatment modality.

Prognostic significance of left ventricular diastolic dysfunction in patients with left ventricular hypertrophy and systemic hypertension (the LIFE Study).

Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension with electrocardiographic LV hypertrophy who underwent echocardiography at baseline and annually thereafter during randomized losartan- or atenolol-based antihypertensive treatment were followed for a mean of 4.6 years. The composite cardiovascular end point was the first occurrence of fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, and cardiovascular mortality. Antihypertensive therapy resulted in an increase in the prevalence of normal transmitral flow pattern from 28% to 46% of patients. Although antihypertensive treatment often resulted in a marked increase in the prevalence of normal mitral valve flow pattern, this was not associated with reduced cardiovascular morbidity and mortality when adjusting for blood pressure, left atrial diameter, LV mass index, and treatment in time-varying Cox analyses. In contrast, lower in-treatment E/A ratios and shorter mitral valve deceleration times were associated with less risk for heart failure. Similarly, normal in-treatment transmitral flow pattern was strongly associated with less risk for heart failure (hazard ratio 0.22, 95% confidence interval 0.05 to 0.98, p = 0.048), even when taking in-treatment left atrial diameter and blood pressure into account. In conclusion, antihypertensive treatment in patients with hypertension with electrocardiographic LV hypertrophy resulted in significant improvement in transmitral flow patterns; this was not associated with reduced cardiovascular morbidity and mortality. However, normal in-treatment LV filling was strongly associated with a reduced risk for hospitalization for heart failure.

In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study.

BACKGROUND: Endocardial fractional shortening (EFS) and midwall shortening (MWS) are impaired in patients with left ventricular hypertrophy. However, it remains unknown whether improvement of left ventricular systolic function during treatment reduces cardiovascular morbidity and mortality in hypertensive patients with preserved left ventricular function. METHODS: Echocardiograms were performed yearly in 840 hypertensive patients with electrocardiographic left ventricular hypertrophy and baseline left ventricular ejection fraction more and equal to 50%. Baseline and annual in-treatment levels of EFS, MWS and blood pressure (BP) were related to occurrence of a composite endpoint (cardiovascular death, myocardial infarction or stroke) and the component endpoints during 3914 patient-years of follow-up. RESULTS: Adjusting for in-treatment BP, left ventricular mass, relative wall thickness and randomized treatments, higher in-treatment EFS was associated with lower risk of myocardial infarction (by 35% per standard deviation [4.5%], P = 0.004) and heart failure (49%, P < 0.001), but in-treatment stress-corrected EFS predicted only incident heart failure (41%, P = 0.014) but not other endpoints. Higher in-treatment MWS tended to be associated with lower risk of composite endpoints (16% per standard deviation [1.8%], P = 0.07) and was significantly associated with myocardial infarction (33%, P = 0.004) and heart failure (43%, P < 0.001). Higher in-treatment stress-corrected MWS was associated with lower rates of myocardial infarction (35%, P = 0.021) and heart failure (50%, P = 0.001). CONCLUSION: These results support a prognostic role for left ventricular myocardial function, as estimated by stress-corrected MWS, during aggressive BP lowering in hypertensive patients with preserved ejection fraction at baseline evaluation.

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy.

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.

Losartan but not atenolol reduce carotid artery hypertrophy in essential hypertension. A LIFE substudy.

BACKGROUND: We wanted to investigate whether treatment with losartan, an angiotensin II receptor blocker, induced regression of carotid artery hypertrophy as compared to the beta-receptor blocker, atenolol. METHODS: In 45 patients recruited for the LIFE Study with stage II-III hypertension and ECG left ventricular (LV) hypertrophy, we measured blood pressure, intima-media thickness (IMT) and lumen in the common carotid arteries by ultrasound, and minimal forearm vascular resistance (MFVR) by plethysmography, after 2 weeks of placebo treatment and after 1, 2 and 3 years of anti-hypertensive treatment with either atenolol- or losartan-based regimens. We measured the same parameters in 26 normal subjects matched for age and gender. RESULTS: The patients had as compared to normotensive controls higher IMT (0.87 vs 0.76 mm, p = 0.001) and intima-media cross-sectional area (IMA) (19.7 vs 15.5 mm2, p<0.001). Systolic and diastolic blood pressures were reduced to the same degree in patients treated with losartan as compared to atenolol. However, IMA decreased significantly only in patients treated with losartan (19.2 vs 17.6 mm2, p = 0.001) and the average relative decrease in IMA during the 3 years of treatment was significantly higher in patients treated with losartan as compared to atenolol (-7.4 vs -2.0%, p<0.05). CONCLUSION: Patients with hypertension and LV hypertrophy had hypertrophy of the common carotid arteries. Losartan, but not atenolol, induced regression of this hypertrophy. Because carotid artery hypertrophy has been associated with strokes, our findings may explain the lower incidence of strokes in the LIFE study in patients treated with losartan as compared to atenolol.

Left ventricular hypertrophy is associated with reduced vasodilatory capacity in the brachial artery in patients with longstanding hypertension. A LIFE substudy.

BACKGROUND: Left ventricular (LV) hypertrophy has been found to be associated with endothelial dysfunction in untreated patients with mild, uncomplicated hypertension. Whether similar relations exist in patients with longstanding hypertension and target organ damage remain to be elucidated. METHODS: In 40 unmedicated, hypertensive patients with electrocardiographic LV hypertrophy we measured 24-h ambulatory blood pressure (n = 37), LV mass index by echocardiography (LVMI(echo)) and magnetic resonance imaging (LVMI(MRI), n = 31), flow-mediated (FMD) and nitroglycerin-induced dilatation (NID) in the brachial artery by ultrasound, acetylcholine- (AIR) and nitroprusside-induced relaxation (NIR) in isolated resistance arteries by wire-myography. RESULTS: LVMI(MRI) correlated negatively to NID (r = -0.60, p < 0.001, n = 30) and to FMD (r = -0.53, p < 0.01, n = 31), but were not significantly correlated to maximal AIR nor NIR. NID (r = -0.53, p < 0.001, n = 36), FMD (r = -0.43, p < 0.01, n = 37), LVMI(MRI) (r = 0.60, p < 0.001, n = 29) and LVMI(echo) (r = 0.39, p < 0.05, n = 37) were all significantly correlated to 24-h systolic blood pressure, whereas maximal AIR and NIR were not. CONCLUSIONS: LV mass was related to NID and FMD, but not to AIR. The relationship to FMD was not independent of NID indicating that LV hypertrophy in patients with longstanding hypertension is more closely related to reduced overall vasodilatory capacity in the brachial artery than to endothelial dysfunction in conduit or subcutaneous resistance arteries. High LV mass and low NID were both related to high blood pressure, suggesting that vasodilatory capacity in conduit arteries is modified parallel to LV geometry by elevated blood pressure.