Treatment of diastolic dysfunction in hypertension.

Diastolic dysfunction is present in half of patients with hypertension and has been shown to be associated with increased cardiovascular morbidity and mortality, as well as the development of heart failure. With the high prevalence of hypertension and its associated complications, treatment of diastolic dysfunction in hypertension is an important and desirable goal. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have been shown to be effective in improvement of measures of diastolic function and are recommended as first-line agents in the control of hypertension in patients with diastolic heart failure. Beta-blockers, calcium channel blockers, and diuretics have also shown some efficacy in improved indices of diastolic filling. However, the independent impact of these pharmacologic interventions on prognosis and outcome in diastolic dysfunction has yet to be clarified. The Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) study, Candesartan in Heart Failure: Assessment in Reduction of Mortality and Morbidity (CHARM-Preserved) trial and the Losartan Intervention For End-point Reduction in Hypertension (LIFE) Study all failed to show improved morbidity and mortality with these drugs although, the LIFE study showed reduced heart failure hospitalization in hypertensive patients with normal in-treatment diastolic function. The Trial Of Preserved Cardiac function heart failure with an Aldosterone anTagonist (TOPCAT) is an on-going large, international study evaluating the effect of spironolactone on cardiovascular mortality, aborted cardiac arrest, or hospitalization for diastolic heart failure. This and other studies will provide further insight into the pathophysiology and management of patients with diastolic dysfunction.

Albuminuria predicts cardiovascular events independently of left ventricular mass in hypertension: a LIFE substudy.

We wanted to investigate whether urine albumin/creatinine ratio (UACR) and left ventricular (LV) mass, both being associated with diabetes and increased blood pressure, predicted cardiovascular events in patients with hypertension independently. After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy with electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured to calculate UACR. The patients were followed for 60+/-4 months and the composite end point (CEP) of cardiovascular (CV) death, nonfatal stroke or nonfatal myocardial infarction was recorded. The incidence of CEP increased with increasing LV mass (below the lower quartile of 194 g to above the upper quartile of 263 g) in patients with UACR below (6.7, 5.0, 9.1%) and above the median value of 1.406 mg/mmol (9.7, 17.0, 19.0%(***)). Also the incidence of CV death increased with LV mass in patients with UACR below (0, 1.4, 1.3%) and above 1.406 mg/mmol (2.2, 6.4, 8.0%(**)). The incidence of CEP was predicted by logUACR (hazard ratio (HR)=1.44(**) for every 10-fold increase in UACR) after adjustment for Framingham risk score (HR=1.05(***)), history of peripheral vascular disease (HR=2.3(*)) and cerebrovascular disease (HR=2.1(*)). LV mass did not enter the model. LogUACR predicted CV death (HR=2.4(**)) independently of LV mass (HR=1.01(*) per gram) after adjustment for Framingham risk score (HR=1.05(*)), history of diabetes mellitus (HR=2.4(*)) and cerebrovascular disease (HR=3.2(*)). (*)P<0.05, (**)P<0.01, (***)P<0.001. In conclusion, UACR predicted CEP and CV death independently of LV mass. CV death was predicted by UACR and LV mass in an additive manner after adjustment for Framingham risk score and history of CV disease.

Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study.

While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrollment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97 mmHg) and men (149/85 from 173/99 mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1 l/min and both -0.20 mmHg/ml/m(2), respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24 g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23 g, P=0.001). LV mass regression was greater in women, by 8.0+/-2.8 g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.

Usefulness of the assessment of the appropriateness of left ventricular mass to detect left ventricular systolic and diastolic abnormalities in absence of echocardiographic left ventricular hypertrophy: the LIFE study.

Conventional definitions of left ventricular (LV) hypertrophy do not account for interindividual differences in loading conditions. We may define LV mass as inappropriately high when exceeding 128% of theoretical values predicted by gender, height(2.7), and stroke work, which explain up to 82% of the variability of LV mass in normal reference subjects. In 652 participants in the Losartan Intervention For Endpoint reduction in hypertension study without clinically overt cardiovascular disease or diabetes, we investigated whether inappropriately high LV mass is associated with relevant LV abnormalities independent of traditional definition of LV hypertrophy (ie, LV mass index >116 g/m(2) in men and >104 g/m(2) in women). The study sample was divided into three groups: patients with inappropriately high LV mass but without LV hypertrophy were compared to patients with LV hypertrophy and to patients with appropriate LV mass and without LV hypertrophy. Patients with inappropriately high but nonhypertrophic LV mass had higher body mass index and relative wall thickness, and lower LV myocardial systolic function, than patients with appropriate LV mass or patients with LV hypertrophy. In multivariate analyses, inappropriately high LV mass was independently associated with lower myocardial systolic function independent of LV hypertrophy and other covariates. Inappropriately high LV mass was also associated with prolonged isovolumic relaxation time and lower mitral E/A ratio independent of covariates. In conclusion, inappropriately high LV mass was associated with relevant, often preclinical, manifestations of cardiac disease in the absence of traditionally defined echocardiographic LV hypertrophy and concentric geometry.

Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy.

Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by ultrasound; and LV mass, relative wall thickness (RWT), systolic function and diastolic filling by echocardiography after two weeks of placebo treatment. LV mass index correlated to IMA/height (r=0.36, P=0.001), serum insulin (r=-0.25, P<0.05), plasma glucose (r=-0.34, P<0.01), and showed a tendency towards a correlation to insulin sensitivity (r=0.21, P=0.051), but was unrelated to MFVR. Deceleration time of early diastolic transmitral flow positively correlated to IMA/height (r=0.30, P<0.01). The ratio between early and atrial LV filling peak flow velocity negatively correlated to MFVR(men) (r=-0.30, P<0.05). Endocardial and midwall systolic LV function were not related to vascular hypertrophy, plasma glucose, serum insulin or insulin sensitivity. In conclusion, insulin resistance was not related to LV hypertrophy or reduced LV function. However, high thickness of the common carotid arteries was associated with LV hypertrophy and high deceleration time of early diastolic transmitral flow. High MFVR was associated with low ratio between early and atrial LV filling peak flow velocity. This may suggest that systemic vascular hypertrophy contributes to abnormal diastolic LV relaxation in patients with hypertension and electrocardiographic LV hypertrophy.

Relation of various degrees of body mass index in patients with systemic hypertension to left ventricular mass, cardiac output, and peripheral resistance (The Hypertension Genetic Epidemiology Network Study).

The impact of different methods of indexation of left ventricular (LV) mass and systemic hemodynamic variables on prevalences and correlates of cardiovascular abnormalities in relation to level of obesity in populations remains unclear. We evaluated 1,672 participants in the Hypertension Genetic Epidemiology Network Study to investigate the relations of overweight and level of obesity to LV mass and prevalences of LV hypertrophy, abnormal cardiac output, and peripheral resistance detected using different indexations for body size. In our study population, 1,577 subjects were clinically healthy nondiabetic hypertensive and 95 were normotensive normal-weight nondiabetic reference subjects. Fat-free mass (FFM) did not differ between the reference group and the normal-weight hypertensive subjects, and increased with overweight. In hypertensive subjects, LV mass and cardiac output increased and total peripheral resistance decreased with overweight. Indexation of LV mass for FFM or body surface area (BSA) resulted in no difference or even lower prevalence of LV hypertrophy in severely obese compared with normal-weight hypertensive subjects. In contrast, indexation of LV mass for height(2.7) identified an increased prevalence of LV hypertrophy with overweight and obesity. Absolute cardiac output increased and total peripheral resistance decreased with overweight. Prevalence of elevated cardiac output indexed for height(1.83) increased and for elevated total peripheral resistance-height(1.83) index decreased with greater overweight, whereas opposite trends were seen when cardiac output and total peripheral resistance were indexed for BSA or FFM. Thus, in hypertensive subjects, FFM increases with overweight and is directly related to LV mass, stroke volume, and cardiac output, and inversely related to total peripheral resistance. Indexations of LV mass and systemic hemodynamics for FFM or BSA obscured associations of LV hypertrophy and abnormal cardiac and total peripheral resistance indexes with overweight, whereas LV mass/height(2,7), cardiac output/height(1.83), and total peripheral resistance-height(1.83) detected significant preclinical cardiovascular abnormalities with obesity.

Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

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.

Left ventricular systolic dysfunction in a biracial sample of hypertensive adults: The Hypertension Genetic Epidemiology Network (HyperGEN) Study.

To determine the prevalence and correlates of left ventricular systolic dysfunction in hypertensive patients in a biracial population-based sample, clinical evaluation and echocardiography were performed in 2086 participants in the Hypertension Genetic Epidemiology Network (HyperGEN) examination; 86% had normal ejection fraction (>54%), 10% had mild ventricular dysfunction (ejection fraction 41% to 54%), and 4% had severe ventricular dysfunction (ejection fraction

Relationship between left ventricular diastolic relaxation and systolic function in hypertension: The Hypertension Genetic Epidemiology Network (HyperGEN) Study.

The relation of impaired left ventricular relaxation, as measured by prolonged isovolumic relaxation time, to ventricular systolic function in hypertension remains uncertain in population-based samples. In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, echocardiograms were analyzed in 1457 hypertensive participants without diabetes, >/=2+ valvular regurgitation, or coronary disease. Impaired relaxation (isovolumic relaxation time >100 ms) was present in 219 (15%) of the participants; they were older and had higher arterial pressure than did those with normal relaxation. Ventricular chamber size, wall thicknesses, mass, and relative wall thickness were greater, and stress-corrected midwall shortening and end-systolic stress/end-systolic volume index were lower with impaired relaxation than with normal relaxation time. Fractional shortening and ejection fraction did not differ between the groups. In logistic regression, the likelihood of prolonged isovolumic relaxation time decreased with higher stress-corrected midwall shortening (odds ratio, 0.97%; 95% confidence interval, 0.96 to 0.99), independently of age, heart rate, and ventricular mass. Neither ejection fraction nor the end-systolic stress/end-systolic volume index was independently related to isovolumic relaxation time. In hypertension, impaired left ventricular relaxation parallels ventricular midwall dysfunction but not systolic chamber function. Whether combined diastolic and systolic dysfunction identifies hypertensive patients at especially high risk of cardiovascular events requires further study.

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.

The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study.

OBJECTIVES: We sought to determine the effect of diabetes mellitus (DM) on left ventricular (LV) filling pattern in normotensive (NT) and hypertensive (HTN) individuals. BACKGROUND: Diastolic abnormalities have been extensively described in HTN but are less well characterized in DM, which frequently coexists with HTN. METHODS: We analyzed the transmitral inflow velocity profile at the mitral annulus in four groups from the Strong Heart Study: NT-non-DM (n = 730), HTN-non-DM (n = 394), NT-DM (n = 616) and HTN-DM (n = 671). The DM subjects were further divided into those with normal filling pattern (n = 107) and those with abnormal relaxation (AbnREL) (n = 447). RESULTS: The peak E velocity was lowest in HTN-DM, intermediate in NT-DM and HT-non-DM and highest in the NT-non-DM group (p < 0.001), with a reverse trend seen for peak A velocity (p < 0.001). In multivariate analysis, E/A ratio was lowest in HTN-DM and highest in NT-non-DM, with no difference between NT-DM and HTN-non DM (p < 0.001). Likewise, mean atrial filling fraction and deceleration time were highest in HTN-DM, followed by HTN-non-DM or NT-DM and lowest in NT-non-DM (both p < 0.05). Among DM subjects, those with AbnREL had higher fasting glucose (p = 0.03) and hemoglobin A1C (p = 0.04). CONCLUSIONS: Diabetes mellitus, especially with worse glycemic control, is independently associated with abnormal LV relaxation. The severity of abnormal LV relaxation is similar to the well-known impaired relaxation associated with HTN. The combination of DM and HTN has more severe abnormal LV relaxation than groups with either condition alone. In addition, AbnREL in DM is associated with worse glycemic control.

Separate and joint effects of systemic hypertension and diabetes mellitus on left ventricular structure and function in American Indians (the Strong Heart Study).

Although the association of systemic hypertension (SH) with diabetes mellitus (DM) is well established, the cardiac features and hemodynamic profile of patients with SH and DM diagnosed by American Diabetes Association criteria have not been elucidated. To address this issue, echocardiograms were analyzed in 1,025 American Indian participants of the Strong Heart Study with neither DM nor SH, 642 with DM alone, 614 with SH alone, and 874 with SH and DM. In analyses that adjusted for age, gender, body mass index, and heart rate, DM and SH were associated with increased left ventricular (LV) wall thicknesses, with the greatest impact of DM on LV relative wall thickness and of the combination of DM and SH on LV mass (both p <0.001). LV fractional shortening was reduced with SH and SH + DM, midwall shortening was reduced with DM, SH, and their combination, and was reduced in both diabetic groups compared with their nondiabetic counterparts (p <0.001). DM alone was associated with lower measures of LV pump performance (stroke volume, cardiac output, and their indexes) than SH alone. Pulse pressure/stroke index, an indirect measure of arterial stiffness, was elevated in participants with DM or SH alone and most in those with both conditions. There were progressive increases from the reference group to DM alone, SH alone, and DM + SH with regard to prevalences of LV hypertrophy (12% to 19%, 29% and 38%) and subnormal LV myocardial function (7% to 10%, 11% and 18%, both p <0.001). In conclusion, DM and SH each have adverse effects on LV geometry and function, and the combination of SH and DM results in the greatest degree of LV hypertrophy, myocardial dysfunction, and arterial stiffness.

Aortic root dilatation at sinuses of valsalva and aortic regurgitation in hypertensive and normotensive subjects: The Hypertension Genetic Epidemiology Network Study .

The association of sinuses of Valsalva dilatation and aortic regurgitation with hypertension is disputed, and few data are available in population-based samples. We explored the relations of sinuses of Valsalva dilatation and aortic regurgitation to hypertension and additional clinical and echocardiographic data in 2096 hypertensive and 361 normotensive participants in the Hypertension Genetic Epidemiology Network study. Age and body surface area were used to predict aortic root diameter using published equations developed from a separated reference population. Aortic dilatation was defined as measured sinuses of Valsalva diameter exceeding the 97.5th percentile of the confidence interval of predicted diameter for age and body size. Aortic dilatation was present in 4.6% of the population. After adjustment for age and body surface area, mean aortic root diameter was larger in hypertensives with suboptimal blood pressure control than normotensives or hypertensives with optimal blood pressure control. In multivariate models, sinuses of Valsalva diameter was weakly positively related to diastolic blood pressure and to left ventricular mass independent of aortic regurgitation. Subjects with aortic dilatation were slightly older, were more frequently men, had higher left ventricular mass, and had lower left ventricular systolic chamber function independent of covariates. Sinuses of Valsalva dilatation was independently related to male gender, aortic valve fibrocalcification, and echocardiographic wall motion abnormalities but not to diastolic blood pressure (or history of hypertension in a separate model). The likelihood of aortic regurgitation increased with larger aortic root diameter, older age, female gender, presence of aortic valve fibrocalcification, and lower body mass index but not hypertension or diabetes. In a subsequent model, diastolic blood pressure was negatively related to aortic regurgitation independent of covariates. In a large population-based sample, sinuses of Valsalva diameter was only mildly larger in subjects with suboptimally controlled hypertension than in normotensives or well-controlled hypertensives, which did not result in differences in prevalence of aortic regurgitation among groups. Sinuses of Valsalva dilatation was associated with higher left ventricular mass and lower systolic function, which may contribute to higher cardiovascular risk in subjects with aortic root dilatation.

Left ventricular function and hemodynamic features of inappropriate left ventricular hypertrophy in patients with systemic hypertension: the LIFE study.

BACKGROUND: Predicted left ventricular (LV) mass for sex, height (2.7), and hemodynamic load can be used as an intrapatient reference for the observed LV mass. The ratio of observed/predicted LV mass may allow more physiologically correct comparisons of LV geometry, systolic and diastolic functions, and hemodynamics among hypertensive patients. METHODS: We studied 659 participants in the LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study with both electrocardiographic and echocardiographic LV hypertrophy (68% of the echocardiographic cohort) without previous myocardial infarction. LV mass was predicted by an equation including sex, stroke work, and height (2.7). Observed/predicted LV mass > 128% defined inappropriate LV hypertrophy (iLVH). Relative wall thickness > or = 0.43 defined concentric LV geometry. Systolic myocardial dysfunction was assessed by midwall mechanics and abnormal LV relaxation by isovolumic relaxation time (IVRT). RESULTS: Compared with patients with appropriate LV hypertrophy (aLVH), those with iLVH had higher body mass index, LV mass index, relative wall thickness, prevalences of systolic myocardial dysfunction and prolonged IVRT and lower end-systolic stress and cardiac index. Patients with eccentric iLVH had the highest wall stress and lowest ejection fraction; 43% had systolic myocardial dysfunction. Of patients with concentric iLVH, 79% had systolic myocardial dysfunction but normal ejection fraction and the lowest wall stress. Systolic myocardial dysfunction was present in 12% with concentric aLVH and none with eccentric aLVH. Prevalence of prolonged IVRT was high in all 4 groups (65% to 77%). Cardiac index was similarly lower with concentric or eccentric iLVH than with aLVH. CONCLUSIONS: Among hypertensives with LV hypertrophy, iLVH identified cardiac phenotypes with a high prevalence of myocardial systolic dysfunction.

Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study.

OBJECTIVES: To clarify the relations of systemic hemodynamics to left ventricular (LV) geometric patterns in patients with moderate hypertension and target organ damage. BACKGROUND: LV geometry stratifies risk in hypertension, but relations of LV geometry to systemic hemodynamic patterns in moderately severe hypertension have not been fully elucidated. DESIGN: Cross-sectional case-control study. SETTING: Baseline findings in the echocardiographic substudy of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE) and in a normotensive reference group. PATIENTS/PARTICIPANTS: Nine hundred and sixty-four patients with Stage I-II hypertension and LV hypertrophy by Cornell voltage duration criteria ((SV3 + RaVL [+ 6 mm in women]) x QRS > 2440 mm x ms) or modified Sokolow- Lyon voltage criteria (SV1 + RV5/RV6 > 38 mm), and 366 apparently normal adults. INTERVENTIONS: None. METHODS: Two-dimensional and Doppler echocardiograms were used to classify hypertensive patients into groups with normal geometry, concentric remodelling and concentric and eccentric hypertrophy, and to measure stroke volume (SV), cardiac output, peripheral resistance and pulse pressure/SV as a measure of arterial stiffness. Comparisons were adjusted for covariates by general linear model with the Sidak post-hoc test RESULTS: Mean SV was higher in patients with eccentric hypertrophy (83 ml/beat) and lower with concentric remodeling (68 ml/beat) than in normal adults (73 ml/ beat). Cardiac output was highest in patients with eccentric LV hypertrophy and lower with concentric remodeling than eccentric hypertrophy; mean pressure and peripheral resistance were equally high in all hypertensive subgroups, whereas pulse pressure/SV was most elevated (by a mean of 47% versus reference subjects) with concentric remodeling and least so (mean + 15%) with eccentric hypertrophy. In multivariate analysis (Multiple R + 0.68), LV mass was independently related to higher systolic pressure, older age, SV, male gender and body mass index (all P< 0.001). Relative wall thickness was independently related (Multiple R + 0.50) to older age, higher systolic pressure, lower SV (all P< 0.001) and higher body mass index (P + 0.007). SV and cardiac output were lower in patients with low stress-corrected midwall shortening. CONCLUSION: In patients with moderate hypertension and ECG LV hypertrophy, the levels of SV and pulse pressure/ SV, are associated with, and may be stimuli to different LV geometric phenotypes.

Effect of type 2 diabetes mellitus on left ventricular geometry and systolic function in hypertensive subjects: Hypertension Genetic Epidemiology Network (HyperGEN) study.

BACKGROUND: Type 2 diabetes is a cardiovascular risk factor. It remains to be elucidated in a large, population-based sample whether diabetes is associated with changes in left ventricular (LV) structure and systolic function independent of obesity and systolic blood pressure (BP). METHODS AND RESULTS: Among 1950 hypertensive participants in the HyperGEN Study without overt coronary heart disease or significant valve disease, 20% (n=386) had diabetes. Diabetics were more likely to be women, black, older, and have higher BMI and waist/hip ratio than were nondiabetics. After adjustment for age and sex, diabetics had higher systolic BP, pulse pressure, and heart rate; lower diastolic BP; and longer duration of hypertension than nondiabetics. LV mass and relative wall thickness were higher in diabetic than nondiabetic subjects independent of covariates. Compared with nondiabetic hypertensives, diabetics had lower stress-corrected midwall shortening, independent of covariates, without difference in LV EF. Insulin levels and insulin resistance were higher in non-insulin-treated diabetics (n=195) than nondiabetic (n=1439) subjects (both P:<0.01). Insulin resistance positively but weakly related to LV mass and relative wall thickness. CONCLUSIONS: In a relatively healthy, population-based sample of hypertensive adults, type 2 diabetes was associated with higher LV mass, more concentric LV geometry, and lower myocardial function, independent of age, sex, body size, and arterial BP. structural and functional abnormalities in addition to, and independent of, atherosclerosis.(13) (14) In the Framingham cohort, diabetes was associated with higher LV mass in women but not men.(15) High blood pressure (BP), obesity, and abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities(16) and may contribute to the association of diabetes with cardiovascular events. Cardiac features of diabetic and nondiabetic hypertensive subjects remain incompletely described in population-based samples. Therefore, we compared clinical and metabolic characteristics, LV geometry, and systolic function between diabetic and nondiabetic hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

Effect of electrocardiographic left ventricular hypertrophy on left ventricular systolic function in systemic hypertension (The LIFE Study). Losartan Intervention For Endpoint.

Left ventricular (LV) ejection fraction is normal in most patients with uncomplicated hypertension, but the prevalence and correlates of decreased LV systolic chamber and myocardial function, as assessed by midwall mechanics, in hypertensive patients identified as being at high risk by the presence of LV hypertrophy on the electrocardiogram has not been established. Therefore echocardiograms were obtained in 913 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiographic (Cornell voltage duration or Sokolow-Lyon voltage) criteria after 14 days' placebo treatment. The 913 patients' mean age was 66 years, and 42% were women. Fourteen percent had subnormal LV endocardial shortening, 24% had subnormal midwall shortening, and 13% had reduced stress-corrected midwall shortening. Nineteen percent had normal LV geometry, 11% had concentric remodeling, 47% had eccentric hypertrophy, and 23% had concentric hypertrophy. LV systolic performance evaluated by LV endocardial shortening and midwall shortening was impaired in 10% of patients with normal geometry, 20% with concentric remodeling, 27% with eccentric hypertrophy, and 42% with concentric hypertrophy. Relative wall thickness, an important independent correlate of LV chamber function, was related directly to endocardial shortening and negatively to midwall shortening and stress-corrected midwall shortening. LV mass was the strongest independent correlate of impaired endocardial shortening, midwall shortening, or both. In hypertensive patients with electrocardiographic LV hypertrophy, indexes of systolic performance are subnormal in 10% to 42% with different LV geometric patterns. Depressed endocardial shortening is most common in patients with eccentric LV hypertrophy, whereas impaired midwall shortening is most prevalent in patients with concentric remodeling or hypertrophy. Thus, in hypertensive patients with electrocardiographic LV hypertrophy, impaired LV performance occurs most often, and is associated with greater LV mass and relative wall thickness and may contribute to the high rate of cardiovascular events.

Maximal exercise capacity is related to cardiovascular structure in patients with longstanding hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.

BACKGROUND: Cardiovascular hypertrophy and remodeling in patients with never-treated hypertension has been associated with impaired exercise capacity, but whether this relationship remains in patients with longstanding hypertension and target organ damage is less elucidated. METHODS: In 43 unmedicated patients with essential hypertension and electrocardiographic left ventricular (LV) hypertrophy, we measured maximal workload and oxygen reserve by bicycle test, 24-h ambulatory blood pressure (BP), LV mass index by magnetic resonance imaging (LVMI(MRI), n = 31), LVMI(echo) and systemic vascular compliance by echocardiography, minimal forearm vascular resistance (MFVR) by plethysmography, and intima media thickness and distensibility in the common carotid arteries by ultrasound. RESULTS: The patients did not achieve the maximal workload as predicted by age, gender and body composition (146[129-163] v 162[146-179] Watt, P = .01). This impaired exercise capacity, calculated as the ratio between achieved and predicted maximal workload, was in simple regression analyses related to lower distensibility of the common carotid artery (r = 0.38, P = .01) and lower oxygen reserve (r = 0.68, P < .001). In multiple regression analyses, lower oxygen reserve was related to higher LVMI(MRI) (beta = -0.44), lower systemic vascular compliance (beta = -0.36), and higher MFVR (beta = -0.52) (adjusted R2 = 0.53, P < .001). CONCLUSIONS: Patients with longstanding hypertension and target organ damage cannot achieve the predicted maximal workload. This impaired exercise capacity was associated with lower common carotid distensibility and lower oxygen reserve. The latter was independently related to LV hypertrophy, low systemic vascular compliance and peripheral vascular remodeling, suggesting that cardiovascular hypertrophy and remodeling may reduce exercise capacity by itself.

Sibling correlation of left ventricular mass and geometry in hypertensive African Americans and whites: the HyperGEN study. Hypertension Genetic Epidemiology Network.

BACKGROUND: Evidence suggests that left ventricular (LV) mass is under genetic control, independently of risk factors known to influence LV size and geometry. METHODS: As part of the HyperGEN study, four field centers recruited African American and white hypertensive siblings (n = 1,664), aged 23 to 87 years. Two-dimensionally guided M-mode echocardiography was performed, and LV mass and relative wall thickness (RWT) were measured at a central reading center. Familial correlations were calculated separately for each ethnic group using maximum likelihood methods, adjusted for the potential confounding influences of age, gender, systolic blood pressure, and obesity. RESULTS: In African Americans, brother-sister, brother-brother, and sister-sister correlation coefficients and standard errors for LV mass were 0.29 (0.08), 0.44 (0.10), and 0.33 (0.05). In whites, the corresponding correlations were lower than in African Americans at 0.05 (0.08), 0.12 (0.11), and 0.22 (0.09), respectively. Sibling correlation of LV geometry, assessed by RWT, was less in African Americans than in whites: brother-sister, 0.04 (0.10) v 0.21 (0.10), brother-brother, 0.12 (0.22) v 0.28 (0.09), and sister-sister, 0.11 (0.07) v 0.19 (0.11). CONCLUSIONS: LV mass is strongly correlated in hypertensive African American siblings, and modestly correlated in their white counterparts, whereas RWT has stronger sibling correlation in whites. The patterns of familial correlation of echocardiographic LV mass and RWT suggest that the genetic underpinnings of LV hypertrophy and geometric remodeling may differ among ethnic groups.

Prevalence and correlates of aortic regurgitation in American Indians: the Strong Heart Study.

OBJECTIVES: We sought to determine the prevalence and correlates of aortic regurgitation (AR) in a population-based sample group. BACKGROUND: Concern over induction of AR by weight loss medication highlights the importance of assessing the prevalence and correlates of AR in unselected patient groups. METHODS: Aortic regurgitation was assessed by color flow Doppler echocardiography in 3,501 American Indian participants age 47 to 81 years during the second Strong Heart Study. RESULTS: Mild (1+) AR was present in 7.3%, 2+ AR in 2.4% and 3+ to 4+ AR in 0.3% of participants, more frequently in those > or =60 years old than in those <60 years old (14.4% vs. 5.8%, p<0.001); AR was unrelated to gender. Compared with participants without AR, those with mild AR had a lower body mass index (p<0.004) and higher systolic pressure (p<0.003). Participants with AR had larger aortic root diameters (3.6+/-0.4 vs. 3.4+/-0.4 cm, p<0.001), higher creatinine levels (1.3+/-1.3 vs. 1.0+/-1.0 mg/dl, p<0.001) and higher urine albumin/creatinine levels (3.6+/-2.3 vs. 3.3+/-2.0 log, p<0.001), as well as higher prevalences of aortic stenosis (AS) or mitral stenosis (MS) (p<0.001). Regression analysis showed that AR was independently related to older age and larger aortic roots (p<0.0001), AS and absence of diabetes (p = 0.002), MS (p = 0.003) and higher log urine albumin/creatinine (p = 0.005). CONCLUSIONS: Aortic regurgitation occurred in 10% of a sample group of middle-aged to older adults and was related to older age, larger aortic root diameter, aortic and mitral stenosis and albuminuria. There was no association of AR with being overweight and a negative association of AR with diabetes.