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Background: Left ventricular wall motion (WM) abnormalities have recognized prognostic significance in patients with coronary or other heart diseases; however, whether abnormal WM predicts adverse events in adults without overt cardiovascular disease has not been assessed. Our objective was to determine whether echocardiographic WM abnormalities predict subsequent cardiovascular events in a population-based sample., Methods and Results: Participants (n=2864, mean age 60+/-8 years, 64% women) without clinically evident cardiovascular disease in the second Strong Heart Study examination who had complete echocardiographic WM assessment were studied. Echocardiographic assessment revealed that 5% of participants (n=140) had focal hypokinesia, and 1.5% (n=42) had WM abnormalities. Relationships between WM abnormalities and fatal and nonfatal cardiovascular events (including myocardial infarction, stroke, coronary artery disease, and heart failure; n=554) and cardiovascular death (n=182) during 8+/-2 years follow-up were examined. In Cox regression, after adjustment for age, gender, waist/hip ratio, systolic blood pressure, and diabetes mellitus, segmental WM abnormalities were associated with a 2.5-fold higher risk of cardiovascular events and a 2.6-fold higher risk of cardiovascular death (both P<0.0001). In similar multivariable models, global WM abnormalities were associated with a 2.4-fold higher risk of cardiovascular events (P=0.001) and a 3.4-fold higher risk of cardiovascular death (P=0.003)., Conclusions: Echocardiographic left ventricular WM abnormalities in adults without overt cardiovascular disease are associated with 2.4- to 3.4-fold higher risks of cardiovascular morbidity and mortality, independent of established risk factors.

Background: Obesity may independently increase the risk of adverse events in hypertension with target-organ damage. We investigated whether body build was independently associated with higher cardiovascular risk and whether treatment with losartan relative to atenolol influenced the impact of body build on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and on cardiovascular death in patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study., Methods and Results: The population of 9079 patients was divided as follows: thin (body mass index [BMI] <20 kg/m2, 2%), normal weight (BMI 20 to 24.9, 24%), overweight (BMI 25 to 29.9, 45%), and obese (class I: BMI 30 to 34.9, 21%; class II: BMI 35 to 39.9, 6%; class III: BMI > or =40, 2%). Incident diabetes increased progressively with BMI and was somewhat higher in the atenolol arm. Differences in gender and race were detected among the body build groups. Rates (Cox proportional hazard analysis) of the primary composite end point did not differ among body build groups after adjustment for age, gender, race, smoking habit, prevalent cardiovascular disease, and left ventricular hypertrophy. Cardiovascular death was more frequent among thin (P<0.05) and pooled class II-III obesity (both P<0.04) than normal-weight groups. Risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan- as opposed to atenolol-based treatment., Conclusions: In the LIFE study, stratification for classes of body build identified increased risk of cardiovascular mortality in both thin and moderately-to-severely obese individuals. This risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan-based treatment as opposed to atenolol-based treatment.

Background: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2))., Methods and Results: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS)., Conclusions: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

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 beta-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: It is unclear whether impairment of left ventricular (LV) diastolic characteristics is independent of systolic dysfunction., Methods and Results: To address this issue, 159 consecutive hypertensive patients (44+/-11 years, 78 obese, 96 women) and 165 normotensive subjects (32+/-11 years, 84 obese, 110 women) were studied with the use of Doppler echocardiography. After adjustment for age, body mass index (BMI), and sex, we found that ejection fraction (EF; M-mode, z-derived) was higher in hypertensive (66. 6+/-5.2%) than in normotensive (63.9+/-4.4%, P<0.0001) subjects, whereas midwall shortening (MS) was lower (hypertensive patients 16. 9+/-2.0%, normotensive subjects 17.8+/-2.2%, P<0.02), even after correction for end-systolic wall stress (P<0.05). Isovolumic relaxation time (IVRT) was greater in hypertensive patients (103+/-14 ms) than in normotensive subjects (78+/-19 ms), as was deceleration time of E velocity and peak A velocity (all P<0.0001). In multivariate analysis, IVRT was unrelated to EF, but a negative relation was found with MS (P<0.001), independent of age, BMI, presence of arterial hypertension, LV geometry, and load (multiple R(2)=0.58). For comparable age, sex distribution, BMI, and blood pressure values, hypertensive patients with lower afterload-adjusted MS exhibited longer IVRT than patients with normal MS (P<0.005). However, IVRT remained higher than in normotensive control subjects after control for LV geometry and load., Conclusions: Doppler indices of delayed LV relaxation can be detected in the presence of normal or supranormal EF but are independently related to impaired MS. A less severely abnormal relaxation, however, can be also detected in the presence of normal midwall function, independent of LV geometry and load. Thus, diastolic abnormalities may occur before systolic dysfunction even when it is measured at the midwall.

Background: Previous studies have identified associations of left ventricular (LV) mass with demographic (body habitus and sex) and hemodynamic variables (blood pressure, stroke volume [SV], and myocardial contractility), but the relative strength and independence of these associations remain unknown., Methods and Results: We examined the relations of echocardiographically determined LV mass to demographic variables, blood pressure, Doppler SV, and measures of contractility (end-systolic stress [ESS]/end-systolic volume index and midwall fractional shortening [MFS] as a percentage of predicted for circumferential end-systolic stress [stress-independent shortening]) in 1935 American Indian participants in the Strong Heart Study phase 2 examination without mitral regurgitation or segmental wall motion abnormalities. Weak positive relations of LV mass with systolic and diastolic pressures (r=.22 and r=.20) were exceeded by positive relations with height (r=.30), weight (r=.47), body mass index (r=.31), body surface area (r=.49), and Doppler SV (r=.50) and negative relations with ESS/volume index ratios (r= -.33 and -.29) and stress-independent MFS (r= -.26, all P<.0001). In multivariate analyses that included blood pressure, SV, and a different contractility measure in each model, systolic pressure, stroke volume, and the contractility measure were independent correlates of LV mass (multiple R=.60 to .66, all P<.0001). When demographic variables were added, LV mass was more strongly predicted by higher SV and lower afterload-independent MFS than by greater systolic pressure, height, and body mass index (each P<.00001, multiple R=.71)., Conclusions: Additional characterization of volume load and contractile efficiency improves hemodynamic prediction of LV mass (R(2)=.30 to .44) over the use of systolic blood pressure alone (R(2)=.05), with a further increase in R(2) to .51 when demographic variables are also considered. However, nearly half of the ventricular mass variability remains unexplained.

Background: An appreciable proportion of asymptomatic hypertensive patients have depressed left ventricular (LV) performance that is identified by midwall shortening/endsystolic stress relations but not by indexes that use endocardial shortening. It has not been established, however, whether depressed midwall ventricular performance has prognostic implications., Methods and Results: Echocardiographic endocardial and midwall LV fractional shortening/circumferential end-systolic stress relations in 294 hypertensive patients were analyzed as predictors of the occurrence of cardiovascular morbid events that occurred in 50 patients (including 14 deaths) during a 10-year mean follow-up. Patients with initially lower midwall but not endocardial shortening, either in absolute terms or as a percentage of predicted from observed end-systolic stress, were more likely to suffer morbid events than those with initially normal values (P < .004). Cardiovascular events occurred in 29 of 100 patients (29%) and death in 10 of 100 patients (10%) among those who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 21 of 194 (11%) and 4 of 194 (2.1%) of the remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3; P < .0001; and odds ratio, 5.3; 95% CI, 1.6 to 17.3; P < .006, respectively). In logistic analysis, increasing age, high LV mass, high systolic blood pressure, and low values for an interaction term between LV mass index and midwall shortening independently predicted cardiovascular events (.04 < P < .001); increasing age, low midwall LV shortening as a percentage of predicted, and high value of the interaction term predicted the occurrence of cardiac death (.004 < P < .0002). Survival analysis controlling for age confirmed that low midwall shortening independently predicted cardiac morbidity or death, especially in the subgroup of patients with LV hypertrophy., Conclusions: Depressed midwall shortening is a predictor of adverse outcome in arterial hypertension; the combination of higher LV mass and lower midwall shortening identifies individuals at markedly increased risk.

Although increased blood viscosity occurs in several cardiovascular diseases, little is known of factors influencing blood rheology in normal adults. Accordingly, we examined the relations of whole blood viscosity (WBV) to its rheologic determinants (hematocrit level, plasma viscosity, protein concentration, and red cell aggregability and rigidity), to demographic and laboratory variables, and to cardiovascular risk factors in 128 normotensive employed adults. Hematocrit levels accounted for 67-84% of variability of WBV at shear rates from 208 to 0.1 sec-1 with lesser contributions from plasma viscosity, red cell aggregability, and rigidity (multiple r = 0.95-0.97); WBV was predicted accurately from standard measurements of hematocrit and total plasma protein levels (multiple r = 0.78-0.92 in "learning" and "test" analysis). Male sex, obesity, dietary Na+ intake, and increasing age had additive effects on WBV (multiple r greater than or equal to 0.59, p less than 0.00001); the last three of these factors and black race independently predicted plasma viscosity (multiple r = 0.36, p less than 0.001). Among regulators of plasma volume, plasma renin activity and urinary Na+ excretion bore independent positive relations to WBV. Diastolic and mean blood pressures were independent predictors of WBV and hematocrit levels (all p less than 0.05). Conventional risk factors (e.g., triglycerides, obesity, and cholesterol levels) were positively related to WBV or plasma viscosity. Thus, in apparently normal adults, 1) WBV or plasma viscosity are increased by male sex, obesity, high sodium intake, aging, and black race, 2) WBV is positively related to plasma renin activity, 3) WBV or plasma viscosity are related to diastolic and mean blood pressures, triglycerides and cholesterol concentrations, and 4) WBV can be predicted from simple measurements of hematocrit and total plasma protein levels.