Research from JAMA — Prognostic Significance of Left Ventricular Mass Change During Treatment of Hypertension — ContextIncreased 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.ObjectiveTo determine whether reduction of LV mass during antihypertensive treatment modifies risk of major CV events independent of blood pressure change.Design, Setting, and ParticipantsProspective 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 MeasuresComposite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke.ResultsThe 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.ConclusionIn 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.

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 ≥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/m ² ; 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.

Background —Although cardiac output (CO) plays the vital role of delivering nutrients to body tissues, few data are available concerning the relations of stroke volume (SV) and CO to body composition in large population samples. Methods and Results —Doppler and 2D echocardiography and bioelectric impedance in 2744 Strong Heart Study participants were used to calculate SV and CO and to relate them to fat-free body mass (FFM), adipose mass, and demographic variables. Both SV and CO were higher in men than women and in overweight than normal-weight individuals, but these differences were diminished or even reversed by normalization for FFM or body surface area. In both sexes, SV and CO were more strongly related to FFM than adipose mass, other body habitus measures, arterial pressure, diabetes, or age. In multivariate analyses using the average of Doppler and left ventricular SV to minimize measurement variability, FFM was the strongest correlate of SV and CO; other independent correlates were adipose mass, systolic pressure, diabetes, age, and use of digoxin and calcium channel and β-blockers. Conclusions —In a population-based sample, SV and CO are more strongly related to FFM than other variables; increased FFM may be the primary determinant of increased SV and CO in obesity.

Background— The epidemic of overweight is increasing the prevalence of both prehypertension and early-onset hypertension, but few population-based data exist on their impact on cardiac structure and function in adolescents and young adults. Methods and Results— We analyzed clinical characteristics, hemodynamic parameters, and left ventricular structure and function in 1940 participants, 14 to 39 years of age, in the Strong Heart Study. Hypertension occurred in 294 participants (15%), who were more often men (70% versus 30%), older (age, 31±7 versus 25±8 years), and more commonly diabetic (23% versus 4.5%; all P <0.001) than their normotensive counterparts. Prehypertension occurred in 675 (35%) of participants with similar trends in gender, age, and diabetes status. After adjustment for covariates, both hypertensive and prehypertensive participants had higher left ventricular wall thickness (0.83 and 0.78 versus 0.72 cm), left ventricular mass (182 and 161 versus 137 g), and relative wall thickness (0.30 and 0.29 versus 0.28 cm) and 3- and 2-fold-higher prevalences of left ventricular hypertrophy than their normotensive counterparts (all P <0.001). Hypertension and prehypertension also were associated with higher mean pulse pressure/stroke volume index (1.24 and 1.15 versus 1.02 mm Hg/mL · m ² ) and total peripheral resistance index (3027 and 2805 versus 2566 dynes · s · cm ⁻⁵ · m ² ; all P <0.001). Conclusions— In a population with high prevalences of obesity and diabetes, hypertension and prehypertension are associated with increases in both cardiac output and peripheral resistance index. Despite the young age of participants with hypertension and prehypertension, they had prognostically adverse preclinical cardiovascular disease, including left ventricular hypertrophy and evidence of increased arterial stiffness.