Vittorio Palmieri

Mitral Ratio of Peak Early to Late Diastolic Filling Velocity as a Predictor of Mortality in Middle-Aged and Elderly Adults: The Strong Heart Study

Background—With aging, left ventricular filling tends to decrease in early diastole, reducing the mitral ratio of peak early to late diastolic filling velocity (E/A). However, the prognostic significance of low or high E/A in older adults remains to be elucidated in population-based samples. Methods and Results—Doppler echocardiograms were analyzed in 3008 American Indian participants in the second Strong Heart Study examination who had no more than mild mitral or aortic regurgitation. Participants were followed for a mean of 3 years after Doppler echocardiography to assess risks of all-cause and cardiac death associated with E/A <0.6 or >1.5; 2429 (81%) participants had normal E/A ratio, 490 (16%) had E/A <0.6, and 89 (3%) had E/A >1.5. All-cause mortality was higher with E/A <0.6 or E/A >1.5 (12% and 13% versus 6%), as was cardiac mortality (4.5% and 6.5% versus 1.6%; both P <0.001). Adjusting for age, sex, body mass index, systolic blood pressure, HDL and LDL cholesterol, smoking, hypertension, diabetes, coronary heart disease, left ventricular hypertrophy, and low ejection fraction (<40%), the relative risk of all-cause death with E/A >1.5 was 1.73 (95% CI, 0.99 to 3.03;P =0.05); the relative risk of cardiac death was 2.8 (95% CI, 1.19 to 6.75;P <0.05). E/A <0.6 was not independently associated with increased all-cause or cardiac mortality (P =0.19 and 0.31, respectively) after adjusting for covariates. Conclusions—In a population-based sample of middle-aged and elderly adults, mitral E/A >1.5 at baseline Doppler echocardiography is associated with 2-fold increased all-cause and 3-fold increased cardiac mortality independent of covariates; mitral E/A <0.6 was also associated with 2-fold increased all-cause and cardiac mortality but not independent of covariates.

Central but not brachial blood pressure predicts cardiovascular events in an unselected geriatric population: the ICARe Dicomano Study.

OBJECTIVES The present study investigated whether central blood pressure (BP) predicts cardiovascular (CV) events better than brachial BP in a cohort of normotensive and untreated hypertensive elderly individuals. BACKGROUND Limited and conflicting data have been reported on the prognostic relevance of central BP compared with brachial BP. METHODS Community-dwelling individuals > or =65 years of age, living in Dicomano, Italy, underwent an extensive clinical assessment in 1995 including echocardiography and carotid ultrasonography and applanation tonometry. In 2003, vital status and CV events were assessed, reviewing the electronic database of the Regional Ministry of Health. Only normotensive (n = 173) and untreated hypertensive subjects (95 diastolic and 130 isolated systolic) were included in the present analysis. RESULTS During 8 years, 106 deaths, 45 of which were cardiovascular, and 122 CV events occurred. In univariate analyses, both central and brachial systolic blood pressure (SBP) and pulse pressure (PP) predicted CV events (all p < 0.005); however, in multivariate analyses, adjusting for age and gender, higher carotid SBP and PP (hazard ratios 1.19/10 and 1.23/10 mm Hg, respectively; both p < 0.0001) but neither brachial SBP nor PP independently predicted CV events. Similarly, higher carotid SBP but not brachial pressures independently predicted CV mortality (hazard ratio 1.37/10 mm Hg; p < 0.0001). CONCLUSIONS Our prospective study in an unselected geriatric population demonstrates superior prognostic utility of central compared with brachial BP.

Reliability of Echocardiographic Assessment of Left Ventricular Structure and Function The PRESERVE Study

OBJECTIVES The study was done to evaluate reliability of echocardiographic left ventricular (LV) mass. BACKGROUND Echocardiographic estimation of LV mass is affected by several sources of variability. METHODS We assessed intrapatient reliability of LV mass measurements in 183 hypertensive patients (68% men, 65 +/- 9 years) enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) trial after a screening echocardiogram (ECHO) showed LV hypertrophy. A second ECHO was repeated at randomization (45 +/- 25 days later). Two-dimensional (2D)-guided M-mode or 2D linear measurements of LV cavity and wall dimensions were verified by one experienced reader. RESULTS Mean LV mass was similar at first and second ECHO (243 +/- 53 vs. 241 +/- 54 g) and showed high reliability as estimated by intraclass correlation coefficient (RHO) = 0.93. Within-patient 5th, 10th, 90th and 95th percentiles of between-study difference in LV mass were -32 g, -28 g, +25 g and +35 g. Mean LV mass fell less from the first to the second ECHO than expected from a formula to predict regression to the mean (2 +/- 19 vs. 17 +/- 12 g, p < 0.001). Reliability was also high for LV internal diameter (RHO = 0.87), septal (RHO = 0.85) and posterior wall thickness (RHO = 0.83). Substantial or moderate reliability was observed for measures of LV systolic function and diastolic filling (RHO from 0.71 to 0.57). CONCLUSIONS Left ventricular mass had high reliability and little regression to the mean; between-study LV mass change of +/-35 g or +/-17 g had > or = 95% or > or = 80% likelihood of being true change.

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.

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.

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.

Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study.

Objective To determine whether combinations of metabolic risk factors (obesity, diabetes and hypercholesterolemia) influence the magnitude of left ventricular (LV) mass and prevalence of LV hypertrophy. Design Cross-sectional, relational. Methods A total of 1627 hypertensive (85.9% treated, 1036 women, 1041 African Americans) and 342 normotensive (180 women, 183 African Americans) participants in the Hyper tension G enetic E pidemiology N etwork (HyperGEN) Study, without prevalent cardiovascular disease, were studied. Echocardiographic LV mass, normalized by height2.7 or fat-free mass or body surface area (BSA) and the ratio of stroke volume to pulse pressure as a percentage of predicted (as a crude estimate of arterial compliance) were analyzed in relation to obesity [by body mass index (BMI)], central fat distribution (by waist circumference), diabetes (by ADA criteria) and hypercholesterolemia. Results Obesity, hypercholesterolemia, and diabetes were more frequent among hypertensives than normotensives (all P < 0.001). After controlling for age, sex, race and type and combination of antihypertensive medication, LV mass/height2.7, but not LV mass/fat-free mass and LV mass/BSA, increased with the number of metabolic risk factors, both in normotensive and hypertensive participants, also after further adjustment for blood pressure (all P < 0.001). Stroke volume/pulse pressure also decreased in hypertensive, but much less in normotensive subjects, with increasing number of metabolic risk factors, independently of relevant confounders (P < 0.0001). Prevalence of LV hypertrophy was predicted by older age, hypertension, central fat distribution, black race and independently increased with the number of associated metabolic risk factors (P < 0.0001). Conclusions The progressive addition of metabolic risk factors including central obesity, diabetes and hypercholesterolemia is associated with higher LV mass normalized by height2.7, independently of hypertension and other important biological covariates. Obesity played a major role in this association. This finding indicates that LV mass is a potentially useful bioassay of strategies of global cardiovascular prevention.

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.

Early abnormalities of cardiac function in non-insulin-dependent diabetes mellitus and impaired glucose tolerance

The aim of this study was to evaluate the role of diabetes and minor abnormalities of glucose homeostasis, such as impaired glucose tolerance, as determinants of cardiac function and structure in a working population. We studied a population-based sample of 64 telephone company employees (both sexes, mean age 58 years): 25 with normoglycemia, 15 with impaired glucose tolerance, and 24 with non-insulin-dependent diabetes mellitus (NIDDM) diagnosed by oral glucose tolerance test according to the recommendations of the World Health Organization. Subjects with myocardial ischemia were excluded. Left ventricular end-systolic dimension, indexed to body surface area, was greater in those with NIDDM (p < 0.05) and in those with impaired glucose tolerance (p < 0.05) with respect to normoglycemic persons. The ratio of the peak early diastolic velocity wave to the late diastolic wave was lower in those with NIDDM (p < 0.05) and in those with impaired glucose tolerance (p < 0.05) than in participants with normoglycemia. Body mass index and blood pressure were similar in the 3 groups. These results clearly indicate that early abnormalities of cardiac structure and function are observed not only in patients with NIDDM, but also in those with impaired glucose tolerance, independent of the confounding role of myocardial ischemia, body weight, and blood pressure.

Change in Diastolic Left Ventricular Filling After One Year of Antihypertensive Treatment

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 r...