Biomedical subjects
Publications and source records attributed to Jonathan N Bella.
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.
The degree to which ethnic differences in left ventricular structure among hypertensive adults are independent of clinical and hemodynamic factors remains uncertain. We assessed whether left ventricular mass and geometry differ between black and white hypertensives after accounting for differences in such factors. Our study group comprised 1060 black and 580 white hypertensive participants free of valvular or coronary disease in a population-based cohort. Blood pressure was measured during a clinic visit and echocardiography was performed using standardized protocols. After controlling for clinical and hemodynamic parameters (cardiac index, peripheral resistance index, and pulse pressure/stroke index), both left ventricular mass and relative wall thickness were higher in blacks than whites (173.9+/-30.9 versus 168.3+/-24.3 grams, P=0.006, and 0.355+/-0.055 versus 0.340+/-0.055 grams, P<0.001). Similarly, the adjusted risk of having left ventricular hypertrophy, whether indexed by height(2.7) or by body surface area, was greater for blacks than for whites (odds ratio: 1.80; 95% CI: 1.29 to 2.51; and odds ratio: 2.50; 95% CI: 1.58 to 3.96, respectively), and this was also true for concentric geometry (odds ratio: 2.28; 95% CI: 1.22 to 4.25). Further adjustment for relatedness in this genetic epidemiological study did not attenuate these differences. Our findings confirm the strong association between black ethnicity and increased left ventricular mass and relative wall thickness in hypertensive adults and demonstrate that these differences are independent of standard clinical and hemodynamic parameters. Whether such differences relate to distinct ambulatory pressure profiles or an ethnic propensity to cardiac hypertrophy requires further investigation.
The metabolic syndrome (MS) is linked to cardiovascular risk. Recently, the Adult Treatment Panel (ATP) III provided new criteria for the definition of the MS. We analyzed the impact of the MS on cardiac structure and function and the independent association of the 5 different components of the ATP III-defined MS with cardiac markers of preclinical disease. Echocardiographic examination was performed in 612 nondiabetic participants with ATP III-defined MS and in 824 participants without the MS. Participants with the MS were more often women (p <0.001) and had similar ages compared with those without the MS. After controlling for confounders, participants with the MS had greater left ventricular (LV) dimension, mass, and relative wall thickness, and left atrial diameter (all p </=0.01), and a higher prevalence of LV hypertrophy (p <0.001), with lower ejection fraction (p <0.05), midwall shortening (p <0.001), and mitral E/A ratio (p <0.05) than participants who did not have the MS. In multiple regression modeling, high blood pressure (BP) and abdominal obesity were the only components of the MS associated with increased LV diameter; only high BP was associated with increased LV mass and prevalence of LV hypertrophy (both p <0.001). When high to normal BP was present in the absence of hypertension, the MS exhibited LV geometry similar to hypertensive participants without the MS. Therefore, abnormal LV geometry and function are related to the MS. Increased BP is the component of the MS most strongly associated with cardiac markers of preclinical disease, even in the absence of traditionally defined hypertension.
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.
BACKGROUND: Left ventricular mass (LVM) exceeding values appropriate for individual workload is associated with concentric LV geometry and systolic dysfunction at both the midwall and chamber levels, even independently of clearcut LV hypertrophy, and is a marker of adverse prognosis. No information is available on whether inappropriate LVM is associated with alterations of LV diastolic properties in unselected population-based studies. METHODS: We examined 1513 hypertensive participants from the HyperGEN population who were without prevalent cardiovascular disease. The LVM prediction from stroke work (systolic blood pressure x Doppler stroke volume), sex, and height (in meters2.7) was derived in 210 nonobese, normal individuals. Observed/predicted LVM >133% defined inappropriate LVM. RESULTS: Participants with inappropriate LVM (229 subjects [15%]) exhibited higher LV dimensions and relative wall thickness, lower ejection fraction, midwall shortening and cardiac output, and prolonged isovolumic relaxation time (IVRT; P < or = .001). Other diastolic abnormalities were not associated with inappropriate LVM. After accounting for demographic and hemodynamic confounders, IVRT was directly related to excess LVM, whereas deceleration time of E velocity was negatively related to excess LVM. Nonechocardiographic correlates of prolonged relaxation included aging, African American ethnicity, male gender, and diabetes. CONCLUSIONS: The LVM exceeding the compensatory needs for workload is associated with delayed LV relaxation as well as mild midwall and chamber systolic dysfunction, independently of demographic, clinical, and hemodynamic confounders. Inappropriately high LVM also correlates with features of increased myocardial stiffness, coexisting with evidence of prolonged LV relaxation.
OBJECTIVE: We sought to determine the heritability of left ventricular dimensions and mass in adult American Indians. METHODS: Echocardiograms were analysed in 1373 American Indian participants, from 445 families, in the Strong Heart Study (SHS) to determine the heritability of left ventricular dimensions and mass. Heritability calculations were performed using variance component analysis in SOLAR, a computer analysis program. RESULTS: The SHS participants analysed in this study included 1305 relative pairs, predominantly (n = 1077) sib-pairs. After simultaneously adjusting for sex, age and centre, the proportion of the residual phenotypic variance due to additive genetic effects or heritability (h2) of left ventricular mass was 0.27 (SE = 0.08, P < 0.001). Addition of body weight, height, systolic blood pressure, heart rate, medications and diabetes into the polygenic model attenuated the residual h2 of left ventricular mass to 0.17 (SE = 0.09, P < 0.05). The residual h2 for left ventricular end-diastolic chamber diameter (LVID), after simultaneously adjusting for sex, age and centre was 0.36 (SE = 0.08, P < 0.001) for the analysed families. The residual h2 for interventricular septal wall thickness was 0.26 (SE = 0.07), while that of left ventricular posterior wall thickness was 0.19 (SE = 0.08, both P < 0.001). While adjustment for body weight, height, systolic blood pressure, heart rate, medications and diabetes reduced the h2 of LVID to 0.33 (SE = 0.09, P < 0.001), the h2 of septal (0.12, SE = 0.10) and posterior wall thickness (0.09, SE = 0.09) were no longer significant after similar adjustment. The residual h2 for relative wall thickness, a measure of left ventricular geometry, was 0.22 (SE = 0.07, P < 0.001) after adjusting for sex, age and centre, and 0.17 (SE = 0.08, P < 0.05) after additional adjustment for body weight, height, systolic blood pressure, heart rate, medications and diabetes. CONCLUSIONS: A substantial proportion of the variance of left ventricular dimensions and mass can be explained by heredity, independent of the effects of sex, age, body size, blood pressure, heart rate, medications and diabetes. Identification of genes influencing left ventricular size and geometry may provide mechanistic and therapeutic targets to prevent left ventricular hypertrophy.
BACKGROUND: Electrocardiographic (ECG) changes during adenosine myocardial perfusion imaging (MPI) correlate with severe coronary artery disease and the presence of collaterals. However, the significance of these changes during adenosine MPI in patients with left ventricular hypertrophy (LVH) on baseline electrocardiogram is less well understood. OBJECTIVE: To evaluate whether ECG changes on adenosine MPI predict ischaemia in patients with LVH. METHODS: We reviewed retrospectively 454 consecutive patients who had undergone adenosine MPI at our institution. The baseline electrocardiogram was reviewed to determine whether or not LVH was present. All patients were administered adenosine at 140 microg x kg x min for a total of 6 min and Tc-sestamibi was injected at 3 min into the protocol. None of the patients underwent any form of exercise during the stress test. RESULTS: Of the 146 patients with LVH, 10 had stress ECG changes suggestive of ischaemia and 40 had evidence of ischaemia on MPI. Similarly, of the 308 patients without LVH, 43 had stress ECG changes suggestive of ischaemia and 68 had ischaemia on MPI. The sensitivity and specificity of stress ECG changes in predicting ischaemia on perfusion in patients with LVH were 12.5% and 95.3%, respectively, with a positive predictive value of 50% and a negative predictive value of 74.3%. CONCLUSION: ECG changes suggestive of ischaemia in patients with LVH are very specific for ischaemia on MPI, and their significance is similar to that in patients without LVH.
OBJECTIVES: We sought to compare systolic and diastolic function in American Indians with diabetes mellitus (DM) based on albuminuria status. BACKGROUND: Albuminuria has been shown to predict cardiovascular disease (CVD) in populations with DM. However, the mechanism of the association of albuminuria and CVD is unclear. METHODS: We compared echo-derived indices of left ventricular (LV) systolic and diastolic function in three groups of American Indians with DM based on albuminuria status: I = no albuminuria (<30 mg albumin/g creatinine); II = microalbuminuria (30 to 300 mg/g); and III = macroalbuminuria (>300 mg/g). RESULTS: Group II and III were slightly older than Group I with no significant gender difference between groups. Systolic blood pressure increased and body mass index decreased from Group I to Group III. Left ventricular systolic function was lower in the groups with albuminuria with step-wise decreases in ejection fraction and stress-corrected midwall shortening (MWS) from Group I to Group III. Similar findings were noted in diastolic LV filling with lower mitral E/A ratios and longer deceleration times in groups with albuminuria. The proportion of participants with abnormal MWS and abnormal LV diastolic relaxation showed step-wise increases from no albuminuria to macroalbuminuria. In multivariate analysis, albuminuria status remained independently associated with both systolic and diastolic dysfunction after adjusting for age, gender, body mass index, systolic blood pressure, duration of diabetes, coronary artery disease, and LV mass. CONCLUSIONS: Albuminuria is independently associated with LV systolic and diastolic dysfunction in type 2 DM; this may explain in part the relationship of albuminuria to increased cardiovascular (CV) events in the DM population. Screening for albuminuria identifies individuals with high CV risk and possible cardiac dysfunction.
BACKGROUND: It has been reported that aortic regurgitation, mitral valve regurgitation, or both are associated with lower body mass index, an index of body adiposity. However, the relations of valvular regurgitation to body composition and myocardial bioenergetic expenditure have not been previously investigated in a population-based sample. METHODS: We selected 1496 patients with hypertension who did not have diabetes mellitus to participate in the Hypertension Genetic Epidemiology Network (HyperGEN) study. We excluded participants with severe aortic or mitral stenosis or with known coronary heart disease. Bioimpedance was used to assess body composition. Echocardiography was used to assess left ventricular (LV) structure and function and to calculate myocardial workload (expressed as energy expenditure) from end-systolic stress, ejection time, and stroke volume. The study sample was divided into groups without mitral or aortic regurgitation (control subjects, n = 1175), with mild valvular regurgitation (1+, n = 246), and with at least moderate (>or=2+) mitral or aortic regurgitation (n = 75). RESULTS: The mean patient age was higher with more severe valvular insufficiency. Sex distribution and blood pressure were similar among the 3 groups. Body mass index and fat mass were significantly lower with more severe valvular regurgitation, whereas fat-free mass was only slightly lower in the group with >or=2+ regurgitation compared with control subjects. Skinfold thicknesses (brachial and subscapular) were lower with more severe valvular regurgitation, whereas self-reported physical activity per week was similar among the 3 groups. LV mass and circumferential end-systolic stress were higher with more severe valvular regurgitation. Noninvasively estimated myocardial energy expenditure was slightly higher in participants with 1+ valvular regurgitation and was significantly higher with >or=2+ regurgitation. Ejection fraction was mildly lower with >or=2+ aortic insufficiency, mitral insufficiency, or both. Midwall shortening and stress-corrected midwall shortening did not differ among groups. CONCLUSIONS: In a population-based sample of adults with hypertension and without diabetes mellitus, known coronary heart disease, or significant valvular stenosis, mitral and aortic regurgitation were associated with higher LV mass and total myocardial biomechanical workload but with lower body fat mass and slightly lower body fat-free mass, which suggests that global myocardial bioenergetic expenditure is elevated by concomitant valvular regurgitation beyond the effect of pressure overload caused by hypertension.
BACKGROUND: Contrast echocardiography (CE) has not gained widespread use despite numerous studies demonstrating its efficacy in the assessment of left ventricular (LV) function. METHODS: We sought to determine whether CE could be used in a high-volume echocardiography laboratory in a clinically effective and time efficient manner. We implemented a protocol with a feasibility phase and an established phase. Cost-benefit analyses were done on the basis of time use. RESULTS: During the feasibility and established phases, data on 119 and 672 patients, respectively, were obtained. After a "sonographer-driven" protocol, contrast studies represented 7% to 8% of the total number of routine transthoracic and stress studies. Stress studies accounted for only 15% of the total number of contrast studies. Obesity was the most common indication for contrast use. LV visualization indices and wall thickening assessment, as evaluated by 2 blinded readers, were significantly improved with CE compared with second harmonic imaging alone. The time to make the decision to use CE and the time taken to administer contrast decreased significantly from the feasibility phase to the established phase (8.3 +/- 5 vs 7.6 +/- 5 min, P <.01, and 13.4 +/- 10 vs 10.2 +/- 5 min, P <.001, respectively). On the basis of time use only, a cost analysis indicated that savings were obtained at a 10-minute reduction in study time. CONCLUSIONS: A "sonographer-driven" CE protocol for LV assessment is feasible in high-volume echocardiography laboratories. It is clinically effective because it significantly improves LV global and regional wall motion visualization. A "sonographer-driven" CE protocol can reduce decision and administration times substantially, thus making CE time-efficient.
OBJECTIVE: To evaluate the relationship between arterial stiffness estimated by the pulse pressure/stroke index ratio (PP/SVi) and prognostically relevant abnormalities of left ventricular geometry and function. METHODS: Baseline data from the echocardiographic substudy of the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study were used. Patients involved in the present study had stage II-III hypertension and electrocardiographic left ventricular hypertrophy; those with a history of coronary heart disease or segmental wall motion abnormalities were excluded. Plasma glucose, total and high-density lipoprotein (HDL) cholesterol and creatinine concentrations and urinary albumin/creatinine were assessed by standard methods. RESULTS: The study sample (n = 667) was subdivided into tertiles of PP/SVi. With greater PP/SVi, age, proportion of women and prevalence of type 2 diabetes, systolic and mean blood pressures were greater, whereas body mass index, body height and diastolic blood pressure were lower. Total and HDL cholesterol, creatinine and albuminuria did not differ among the three groups. After adjustment for age, sex and body size, greater PP/SVi was related to concentric left ventricular geometry, but showed a weak negative relationship to left ventricular mass and aortic root diameter; the prevalence of aortic fibrocalcification and left atrial diameter did not differ among tertiles of PP/SVi. PP/SVi was related to greater left ventricular end-systolic stress; stress-corrected left ventricular chamber function was greater with greater PP/SVi, whereas myocardial contractility did not differ significantly among the three groups. Greater PP/SVi was related to greater mitral E-wave/A-wave ratio and shorter isovolumic relaxation time independently of age, sex, left ventricular geometry, systolic function and other confounders. CONCLUSION: Increased estimated arterial stiffness is associated with concentric left ventricular geometry and with diastolic left ventricular abnormalities suggestive of increased diastolic left ventricular stiffness.
OBJECTIVES: To evaluate the differences between using height(2.7) or fat-free mass for assessment of the appropriateness of left ventricular mass (LVM) in relation to hemodynamic load, and to evaluate the performance of Doppler as compared with M-mode-derived stroke volume for computation of predicted values of LVM. DESIGN: Cross-sectional. SETTING: Population-based. PARTICIPANTS: We studied 2299 participants from the Hypertension Genetic Epidemiology Network Study (prevalent cardiovascular disease in 342). OUTCOME MEASURES: Individual predicted values of LVM were generated by equations using sex, stroke work (systolic blood pressure x stroke volume by either Doppler or M-mode) and either height(2.7) or fat-free mass, as measures of body build, in 228 normotensive, non-obese, non-diabetic participants. Observed LVM was divided by the predicted value and evaluated as 'excess of LVM'. RESULTS: Among 1957 participants without prevalent cardiovascular disease, obese individuals (n = 1008) were slightly younger than non-obese individuals, whereas diabetic participants (n = 294) were slightly older. Excess of LVM was positively related to body mass index (BMI), independently of echocardiographic method and measure of body build, especially when height(2.7) and m-mode stroke work were used, and was greatest in the presence of concentric left ventricular hypertrophy (P < 0.0001). Excess LVM by height(2.7) was progressively greater than that by fat-free mass, as BMI increased (P < 0.0001). In analyses of covariance of association of prevalent cardiovascular disease with age, sex, race, BMI, and excess of LVM (by each method), methods using height(2.7) were more associated with prevalent cardiovascular disease than were methods using fat-free mass (P < 0.02). CONCLUSIONS: Deviation of LVM from values that compensate hemodynamic load can be similarly identified using different measures of body build and methods to generate stroke work. However, the use of height(2.7) to compute LVM as a percentage of that predicted appears to identify deviations from compensatory values that are independently related to prevalent cardiovascular disease more effectively than does the use of fat-free mass.
There is limited information on correlates of left ventricular wall motion (WM) abnormalities in ambulatory patients with hypertension and ECG left ventricular hypertrophy by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria. Therefore, we assessed the prevalence and the correlates of echocardiographic global and segmental left ventricular WM abnormalities in 942 hypertensive patients with hypertrophy enrolled in the Losartan Intervention For End-point reduction in hypertension (LIFE) echo substudy. Patients were separated into groups of those with normal WM or those with segmental or global WM abnormalities. Segmental and global WM abnormalities were mostly of mild degree and were detected in 7% and 6% of the study sample. Compared with subjects with normal motion, those with WM abnormalities were mostly men and had higher prevalences of self-reported coronary heart disease, ECG signs of myocardial infarction, ST-strain pattern, and higher Cornell voltage-duration product, echo-left ventricular mass, and albuminuria, but lower total and high-density lipoprotein cholesterol. Blood pressure was similar among groups. No significant differences were found between patients with global or segmental WM abnormalities. Only half of patients with WM abnormalities had a history or ECG signs of coronary heart disease. Independent correlates of WM abnormalities were higher albuminuria and Cornell voltage-duration product, male gender, and echo-left ventricular hypertrophy, but lower cholesterol. In a subanalysis restricted to patients with WM abnormalities, those with evident cardiovascular disease had a higher prevalence of ST-strain pattern than those with subclinical WM abnormalities, but other clinical, ECG, or echocardiographic parameters were indistinguishable between the 2 groups. Thus, in hypertensives with ECG left ventricular hypertrophy, WM abnormalities, mostly of mild degree, occurred in one eighth of the patients and were associated with male gender, left ventricular hypertrophy, and albuminuria. No significant differences were found between patients with global or segmental wall motion abnormalities.
OBJECTIVE: To evaluate in adults with type 2 diabetes the extent to which the relation of left ventricular hypertrophy (LVH) to markers of systemic inflammation (fibrinogen and high-sensitivity C-reactive protein [hsCRP]) are affected by microangiopathy. RESEARCH DESIGN AND METHODS: We selected adults with type 2 diabetes using American Diabetes Association criteria from a population-based cohort, excluding those with medical history or electrocardiographic evidence of coronary heart disease or dialysis-dependent renal failure. LVH was assessed by echocardiogram. RESULTS: Of the 1299 eligible participants, 384 (29.6%) had LVH, which was associated with higher BMI, hsCRP, fibrinogen, and albuminuria in univariate analyses. After controlling for significant confounders, fibrinogen and albuminuria were higher in the presence of LVH (both P < 0.01), whereas hsCRP was not (P = 0.2), mostly because of the confounding effect of BMI. Adjustment for albuminuria abolished the relation of LVH to higher fibrinogen (P = 0.2). However, fibrinogen was significantly higher in participants with LVH among those without pathologic levels of albuminuria (<30 mg/g creatinuria), but not independent of BMI. Although hsCRP and fibrinogen were moderately correlated, fibrinogen, but not CRP, showed a significant relation with albuminuria. CONCLUSIONS: In adults with type 2 diabetes, echocardiographic LVH is associated with susceptibility to atherothrombosis and increased albuminuria, which is a marker of microangiopathy and endothelial dysfunction that appears in turn to be a relevant pathogenetic link between LVH and inflammation. However, in the absence of significant microalbuminuria, elevated BMI is a relevant pathogenetic factor in the relation of LVH to increased levels of markers of inflammation, potentially preceding development of significant albuminuria. In the presence of microangiopathy, we found that the atherothrombotic risk profile associated with LVH was independent of BMI and possibly reflected the association of LVH with a higher degree of endothelial dysfunction.
BACKGROUND: Left ventricular (LV) hypertrophy is an independent predictor of increased morbidity and mortality. However, whether assessment of LV mass and geometry by cardiac single photon emission computed tomography (SPECT) is feasible remains unclear. MATERIAL/METHODS: We compared LV mass and geometry measured by cardiac SPECT to standard echocardiography in thirty consecutive patients (female 73%n mean age 22.64+/-17 years) who had both cardiac SPECT and echocardiography done less than 1 week apart. RESULTS: There was good correlation between the LV mass (r=0.73, p <0.001) and relative wall thickness (r=0.50, p<0.01) derived by cardiac SPECT to those of standard echocardiography. Using Bland-Altman method, the 95% confident interval of agreement between cardiac SPECT and standard echocardiography ranged from -52 g (5th percentile) to 124 g (95th percentile, mean difference =36+/-45) for LV mass and from -1 (5th percentile) to -0.6 (95th percentile, mean difference =-0.8+/-0.1) for relative wall thickness. CONCLUSIONS: Assessment of left ventricular mass and geometry using cardiac SPECT is feasible and may provide prognostic information beyond measurement of perfusion and function.
PURPOSE: Previous studies of the association between the use of appetite suppressants and valvular heart disease have not accounted for the effects of valvular structure and aortic root diameter, which are associated with obesity. We assessed whether the use of the appetite suppressants fenfluramine/dexfenfluramine, either alone or with phentermine, was associated with aortic regurgitation while adjusting for these variables. SUBJECTS AND METHODS: The sample included 2524 adult participants in the population-based Hypertension Genetic Epidemiology Network study. Information regarding current drug use was assessed during a clinical examination. Medication use was continued at the time of echocardiographic study. Expert readers blinded to current therapy read echocardiograms centrally at Cornell Medical Center. Analyses of the associations between use of fenfluramine/dexfenfluramine (alone or with phentermine) and aortic regurgitation adjusted for potential confounders, including aortic root dilatation and valve fibrocalcification. RESULTS: Nineteen participants, all of whom had hypertension, were being treated with fenfluramine or dexfenfluramine (5 on these agents alone, 14 also with phentermine). Aortic regurgitation was present in 32% (n = 6) of those taking fenfluramine or dexfenfluramine versus 6% (162/2505) of remaining subjects (P = 0.001). In multivariate-adjusted analyses, treatment with fenfluramine or dexfenfluramine was associated with aortic regurgitation (odds ratio [OR] = 4.9; 95% confidence interval [CI]: 1.7 to 14) and aortic fibrocalcification (OR = 5.2; 95% CI: 1.9 to 15). CONCLUSION: In a population-based sample, use of fenfluramine or dexfenfluramine, alone or in combination with phentermine, was associated with aortic regurgitation independent of aortic dilatation or fibrocalcification.
Aortic root dilatation is a major pathophysiological mechanism for aortic regurgitation and predisposes the aortic root to dissection or rupture. However, only a small proportion of the variance of aortic root size can be explained by its known clinical and demographic correlates. The present study was undertaken to determine the heritability of echocardiographically derived aortic root diameter in the American Indian participants in the second Strong Heart Study examination. Echocardiograms were analyzed in 1373 SHS participants who had > or =1 family member in the cohort. Heritability calculations were performed by using variance component analysis as implemented in SOLAR, a computer analysis program. In a polygenic model, the variables entered and identified as covariates of larger aortic root diameter were older age, male sex, and center (P<0.001), which accounted for 35% of the overall variability of aortic root diameter. After simultaneous adjustment was made for these significant covariates, the proportion of phenotypic variance due to additive genetic contribution or residual heritability (h2) was 0.51 (SE=0.08, P<0.001). Additionally, simultaneous adjustment for height, weight, and systolic and diastolic BPs yielded slightly lower residual h2 of aortic root diameter (h2=0.44, SE=0.08, P<0.001), which accounted for 26% of the overall variance of aortic root size. Because center effects were identified as significant covariates in the analyses, h2 analyses were performed separately in Arizona, Oklahoma, and North/South Dakota centers, which confirmed that a significant proportion of the phenotypic variance of aortic root diameter is due to additive genetic contribution. Heredity explains a substantial proportion of the variability of aortic root size that is not accounted for by age, sex, body size, and blood pressure. Echocardiographic screening of family members with aortic root dilatation may identify other individuals predisposed to aortic dissection or rupture.
Although several studies indicate that there are gender differences in left ventricular (LV) systolic function, it remains unclear whether similar differences exist with regard to diastolic function. Accordingly, Doppler echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%) hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study with no evidence of abnormal wall motion or significant valvular heart disease. There was no difference in age between genders, but after adjusting for age and race, men had lower body mass indexes (29.8 +/- 5.2 vs 32.3 +/- 7.6 kg/m(2)) and heart rates (67 +/- 12 vs 69 +/- 11 beats/min) and higher systolic and diastolic blood pressures (BP) than women (134 +/- 20 vs 130 +/- 21 and 80 +/- 11 vs 72 +/- 11 mm Hg, all p <0.001). LV mass/height(2.7) was slightly greater in women than in men (43 +/- 10 vs 42 +/- 9 g/m(2.7), p <0.05). After adjusting for age, race, systolic BP, body mass index, heart rate, and LV hypertrophy, both mitral E-wave (70 +/- 18 vs 77 +/- 19) and A-wave (74 +/- 15 vs 79 +/- 17, both p <0.001) velocities were lower in men than in women, but the mitral E/A ratio and atrial filling fraction were nearly identical in both genders. Deceleration time (221 +/- 55 vs 214 +/- 46 cm/s, p = 0.018) and isovolumic relaxation time (IVRT) were longer in men than in women (85 +/- 18 vs 81 +/- 17 cm/s, p <0.001). Prolonged IVRT was present in more men than women (14% vs 7%, p <0.05). In analyses of covariance, adjusting for age, race, systolic BP, body mass index, heart rate, and medications, male gender remained related to prolonged deceleration time and IVRT. Thus, in this population-based sample of hypertensive adults, men had evidence of slower early diastolic LV filling than women. This gender difference in diastolic function may provide insight into gender differences in congestive heart failure and other specific cardiovascular diseases.