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Jonathan N Bella

Publications and source records attributed to Jonathan N Bella.

At least 19 recordsLinked to original sources
PubMed2007

Genome-wide linkage mapping for valve calcification susceptibility loci in hypertensive sibships: the Hypertension Genetic Epidemiology Network Study.

It remains unclear whether genetic factors contribute to the susceptibility to valve calcification. Accordingly, echocardiograms and genotyping were performed in 1871 hypertensive siblings who participated in the Hypertension Genetic Epidemiology Network Study. Genome-wide affected sibpair nonparametric linkage analysis was conducted using the allele-sharing method implemented in the Merlin computer program. A total of 1014 sibships from 858 families were evaluated for aortic valve sclerosis or mitral annular calcification. Of these, 78 sibships from 68 families contained > or =2 affected siblings with > or =1 type of valve calcification (142 affected siblings). All 3 of the traits showed a modest degree of familial aggregation, with sibling recurrence risk (SD) and sibling recurrence risk ratio (95% CI) being 0.25 (0.035) and 2.31 (1.72 to 3.11) for aortic valve sclerosis, 0.25 (0.035) and 1.78 (1.36 to 2.33) for mitral annular calcification, and 0.31 (0.030) and 1.52 (1.24 to 1.85) for aortic valve sclerosis and mitral annular calcification, respectively. Affected sibpair linkage analysis revealed the highest logarithm of odds score (3.14) in chromosome 16 at 105.6 cM for aortic valve sclerosis. Other chromosomal regions with logarithm of odds score > or =1.9 were found in chromosomes 19 (2.88), 16 (2.63), 1 (2.12), and 2 (2.03) for aortic valve sclerosis and chromosome 13 (2.12) for any valve calcification. There was no logarithm of odds score > or =1.9 for mitral annular calcification. Our study shows strong linkage of aortic valve sclerosis to chromosome 16q22.1-q22.3 and suggestive linkage to chromosome 19p13.11-p11 and identifies several other promising genomic regions that may contain specific susceptibility loci for valve calcification.

Adult↗
PubMed2006

Gender differences in left ventricular systolic function in American Indians (from the Strong Heart Study).

Data from population-based studies indicate that men have a higher incidence and worse prognoses of congestive heart failure than women. Echocardiography was used to compare left ventricular (LV) myocardial and chamber contractility between 490 male and 861 female American Indian participants in the second Strong Heart Study examination. After adjusting for fat-free mass, baseline hypertension, diabetes mellitus, coronary heart disease, and alcohol consumption, LV ejection fractions were higher in women than men (66 +/- 8% vs 63 +/- 9%, p = 0.002), as were stress-corrected mid-wall shortening (106 +/- 13% vs 104+/-15%, p = 0.006) and the circumferential end-systolic stress/end-systolic volume index (7.1 x 10(4) +/- 1.9 x 10(4) vs 6.5 x 10(4) +/- 2.1 x 10(4) kdyne/cm3, all p values <0.001). LV ejection fractions were less than the predefined partition value in 4.7% of women and in 16.7% of men (odds ratio 0.25, 95% confidence interval 0.18 to 0.34, p <0.001). Stress-corrected mid-wall shortening was less than the predetermined lower limit of normal in 2.9% of women and in 6.2% of men (odds ratio 0.45, 95% confidence interval 0.29 to 0.70, p <0.001). There was no significant gender difference in supranormal function by either measure of LV systolic function. Estimated mean independent effects of female gender were a 3% greater ejection fraction, 2.7% greater stress-corrected mid-wall shortening, and a 0.4 x 10(4) kdyne/cm3 greater circumferential end-systolic stress/end-systolic volume index. In conclusion, in a population-based sample aged 45 to 74 years, women had greater LV myocardial and chamber function than men. Gender-specific partition values for measures of LV systolic function may be necessary to detect abnormal contractility in clinical and epidemiologic studies.

Aged↗
PubMed2006

Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS).

BACKGROUND: Echocardiographic left atrial (LA) volume has been documented to be an independent predictor of cardiovascular events. Less is known about the predictive ability of anteroposterior LA diameter, a simpler measure of LA size obtained routinely during echocardiographic evaluation. METHODS: We investigated the prognostic value of LA diameter for incident cardiovascular events in 2804 American Indians free of clinical cardiovascular disease, valvular disease, and atrial fibrillation. Echocardiographic variables were obtained using standardized methods, and previously derived sex-specific partition values were used to define left ventricular (LV) hypertrophy indexed to height(2.7) (in meters) and LA enlargement (> 4.2 cm in men, > 3.8 cm in women). Cardiovascular events included nonfatal stroke, coronary heart disease, congestive heart failure, and fatal cardiovascular disease based on validated definitions. RESULTS: During a median follow-up of 7 years, 368 events occurred. LA diameter, both as a continuous and as a categorical variable, was significantly associated with incident cardiovascular events in unadjusted analyses. In multivariable analyses that adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol-high-density lipoprotein cholesterol, smoking, renal insufficiency, LV hypertrophy, abnormal LV systolic and diastolic function, mitral annular calcification, fibrinogen, and C-reactive protein, both LA diameter (risk ratio 1.04/mm, 95% CI 1.02-1.07, P < .002) and LA enlargement (risk ratio 1.57, 95% CI 1.17-2.10, P = .002) remained independent predictors of first cardiovascular events. CONCLUSIONS: In this population-based cohort, LA diameter independently predicted incident cardiovascular events after adjustment for established clinical, echocardiographic, and inflammatory risk factors. This simple measure of LA dilatation can identify individuals at heightened risk who may warrant more aggressive risk factor modification.

Aged↗
PubMed2006

Association of pulse pressure with cardiovascular outcome is independent of left ventricular hypertrophy and systolic dysfunction: the Strong Heart Study.

BACKGROUND: Whether increased pulse pressure (PP) predicts cardiovascular (CV) events independent of left ventricular hypertrophy (LVH) and systolic dysfunction is unclear. METHODS: Strong Heart Study adults (2946) without clinically overt coronary heart disease were studied. Echocardiographic LV mass >49.2 g/m(2.7) in men or >46.7 g/m(2.7) in women defined LVH. Clinical, metabolic, and echocardiographic characteristics were evaluated among participants divided in quartiles of PP (cut points: 42, 52, and 64 mm Hg). Mean follow-up for evaluation of all-cause and CV mortality was approximately 7 years. RESULTS: Mean age, proportion of women, and proportion of participants with diabetes increased across quartiles of PP. Partially by definition, the proportion of participants with hypertension was also higher with wider PP. Systolic and mean blood pressure (BP) increased whereas diastolic BP did not differ significantly across quartiles of PP. The LV mass index was higher whereas ejection fraction (EF) tended to be lower with wider PP. The CV mortality and all-cause mortality were higher in the highest quartile of PP. Wider PP predicted CV mortality independently of traditional risk factors, LVH and reduced EF. CONCLUSIONS: Wider PP was associated with a higher hazard ratio of CV mortality independent of traditional CV risk factors, LVH and reduced EF in adults without overt coronary heart disease.

Aged↗
PubMed2006

Electrocardiographic strain pattern and left ventricular diastolic function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

BACKGROUND: Whether the typical electrocardiographic (ECG) strain pattern (Strain, in leads V5 and/or V6), which is associated with left ventricular hypertrophy (LVH) and LV systolic dysfunction, is independently associated with LV diastolic dysfunction is unknown. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study enrolled hypertensive patients with ECG-LVH, of whom 10% underwent Doppler echocardiography. LV diastolic function measures included peak mitral E and A wave velocities and their ratio (E/A); E wave deceleration time (EDT); atrial filling fraction (AFF); and isovolumic relaxation time (IVRT). Normal filling pattern was defined by E/A < 1 with EDT >or= 150 and or=60 ms; abnormal relaxation by E/A < 1 with EDT > 250 ms or IVRT > 100 ms; pseudonormal filling pattern by E/A >or= 1 associated with IVRT > 100 ms or EDT > 250 ms; restrictive pattern by E/A >or= 1 with IVRT < 100 ms and EDT < 250 ms. A combined index of LV systolic-diastolic function was also computed (isovolumic time/ejection time, modified myocardial performance index). Of LIFE echo substudy participants with all needed ECG and Doppler data (n = 791), 110 (14%) had Strain. RESULTS: Strain was associated with male gender, African-American race, diabetes, history of coronary heart disease (CHD), higher systolic blood pressure (BP), LV mass and relative wall thickness, and higher prevalences of echo-LV hypertrophy and wall motion abnormalities, and with slower heart rate (all P < 0.05). Age, diastolic BP and LV ejection fraction were similar in patients with or without Strain. Diastolic parameters, and prevalences of different LV filling patterns, did not differ significantly between patients with versus those without Strain (all P > 0.1), but modified myocardial performance index was higher with Strain (P < 0.05). Findings were consistent in multivariate analyses. The association of Strain with higher modified myocardial performance index was no longer statistically significant after accounting for LV systolic function and wall motion abnormalities. CONCLUSIONS: In hypertensive patients with ECG-LVH, the ECG Strain pattern did not identify independently those with more severe LV diastolic abnormalities.

Aged↗
PubMed2005

BDNF-mediated enhancement of inflammation and injury in the aging heart.

Aging is associated with shifts in autocrine and paracrine pathways in the cardiac vasculature that may contribute to the risk of cardiovascular disease in older persons. To elucidate the molecular basis of these changes in vivo, phage-display biopanning of 3- and 18-mo-old mouse hearts was performed that identified peptide epitopes with homology to brain-derived neurotrophic factor (BDNF) in old but not young phage pools. Quantification of cardiac phage binding by titration and immunostaining after injection with BDNF-like phage identified a twofold increased density of the BDNF receptor, truncated Trk B, in the aging hearts. Studies focused on the receptor ligand using a rat model of transient myocardial ischemia revealed increases in cardiac BDNF associated with local mononuclear infiltrates in 24- but not 4-mo-old rats. To investigate these changes, both 4- and 24-mo-old rat hearts were treated with intramyocardial injections of BDNF (or PBS control), demonstrating significant inflammatory increases with activated macrophage (ED1+) in BDNF-treated aging hearts compared with aging controls and similarly treated young hearts. Additional studies with permanent coronary occlusion following intramyocardial growth factor pretreatment revealed that BDNF significantly increased the extent of myocardial injury in older rat hearts (BDNF 35 +/- 10% vs. PBS 16.2 +/- 7.9% left ventricular injury; P < 0.05) without affecting younger hearts (BDNF 15 +/- 5.1% vs. PBS 14.5 +/- 6.0% left ventricular injury). Overall, these studies suggest that age-associated changes in BDNF-Trk B pathways may predispose the aging heart to increased injury after acute myocardial infarction and potentially contribute to the enhanced severity of cardiovascular disease in older individuals.

Aging↗
PubMed2005

Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy).

This study investigated whether aortic valve (AV) sclerosis was associated with traditional cardiovascular (CV) risk factors and CV events in hypertensive patients with electrocardiographic left ventricular (LV) hypertrophy, as previously demonstrated in the general population. AV sclerosis was associated with several CV risk factors and predicted CV events independently of prevalent CV disease and traditional CV risk factors, including LV mass and ejection fraction.

Aged↗
PubMed2005

Normalization for body size and population-attributable risk of left ventricular hypertrophy: the Strong Heart Study.

BACKGROUND: Left ventricular hypertrophy (LVH) is identified by left ventricular mass (LVM) normalized by body surface area (BSA) or height (in meters) also raised to allometric powers. The presence of LVH detected by these indices predicts increased cardiovascular (CV) events. Whether different indexations of LVH differ in their ability to predict excess risk is unknown. METHODS: A total of 2400 subjects, (1589 women and 811 men), 59 +/- 8 years of age and without prevalent CV disease, valve disease or wall motion abnormalities and high prevalence of obesity were followed for an average of 86 months. Reference values (mean +/- 1.96 SD) for LVM/BSA, LVM/BSA(1.5), LVM/m, LVM/m(2.7), and LVM/m(2.13) were obtained in 251 normal participants and population-attributable risk percent (PAR%) for fatal and nonfatal CV events were calculated from prevalence of LVH and hazard ratios (HR). RESULTS: In the entire population or in hypertensive participants, prevalence of LVH was higher for LVM/m(2.7) (20% and 28%) and LVM/m(2.13) (18% and 25%) than for BSA (7% and 11%). Age and sex-adjusted PAR% for LVM/m(2.7) or LVM/m(2.13) were on average 1.8-fold greater than for LVM/BSA in the entire population, and 1.6-fold greater in hypertensive participants, differences that were statistically significant. CONCLUSIONS: The presence of LVH identified by LVM normalized for height to allometric powers is associated with a higher proportion of incident CV events than is LVH detected by normalization for BSA and is convenient for identification of individuals at high risk and in need of preventive intervention in populations with high prevalence of obesity. Allometric power methods allow detection of prognostically adverse, obesity-related LVH, which is unidentified using BSA.

Body Height↗
PubMed2005

Left atrial systolic force and cardiac markers of preclinical disease in hypertensive patients: the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

BACKGROUND: Left atrial systolic force (LASF) has been recently reported to be associated with prolonged left ventricular (LV) relaxation and concentric LV geometry in a clinical setting. This study analyzes the association of increased LASF to LV geometry and function in hypertensive patients from a population study. METHODS: Doppler echocardiographic findings were examined in 684 subjects with treated hypertension and without prevalent cardiovascular disease from the Hypertension Genetic Epidemiology Network (HyperGEN) Study (426 African American, 448 female, 125 diabetic, 174 obese; age 53.8+/-10.8 years). The LASF was assessed from the mitral orifice area and pulse-wave Doppler peak A flow velocity. The LASF was defined as being high if >14.33 kdynes (90th percentile of the normal distribution in 246 normal adults). RESULTS: The LASF was high in 269 participants (39.3% of study population), who were older and had higher mean body mass index (all P<.01). Participants with high LASF had higher systolic BP and heart rate (both P<.01) but similar diastolic BP. After controlling for covariates, participants with high LASF exhibited higher LV dimensions and mass than those with normal LASF (all P<.01). The prevalence of LV hypertrophy was also higher (P<.001). Participants with high LASF exhibited normal ejection fraction, higher stroke volume, cardiac output, E and A velocities, slower E deceleration, and lower E/A ratio than those with normal LASF (all P<.01). CONCLUSIONS: Enhanced LASF is associated with LV hypertrophy, normal LV chamber function, increased cardiac output, and prolonged relaxation. The LASF is a preload-dependent measure.

Adult↗
PubMed2005

Aortic valve sclerosis and albuminuria predict cardiovascular events independently in hypertension: a losartan intervention for endpoint-reduction in hypertension (LIFE) substudy.

BACKGROUND: Aortic valve (AV) sclerosis and urine albumin/creatinine ratio (UACR) are both markers of atherosclerosis. We aimed to investigate whether they predicted cardiovascular (CV) events independently in patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy. METHODS: After 2 weeks of placebo treatment, clinical, laboratory, and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy who had electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured calculating UACR. The presence of AV sclerosis was defined as valve thickening or calcification. Fifteen patients with mild AV stenosis were excluded. The patients were followed for 60 +/- 4 months and the composite endpoint (CEP) of CV death, nonfatal stroke, or nonfatal myocardial infarction was recorded. RESULTS: A value of UACR above the median value of 1.406 was associated with higher incidence of CEP and CV death in patients with AV sclerosis (CEP: 18.8% v 9.0% P < 0.05, CV death: 7.1% v 0.7% P < 0.01) and in patients without AV sclerosis (CEP: 14.0% v 4.9% P < 0.001, CV death: 5.1% v 1.1% P < 0.01). In Cox regression analysis, AV sclerosis predicted CEP (hazard ratio [HR] = 1.52, P < .05), but not CV death (HR = 1.30 [0.62 to 2.70], NS) independently of logUACR (HR = 1.70 and HR = 3.25, both P < .001). After adjusting for the Framingham Risk Score, CV disease, diabetes, smoking, and treatment allocation, AV sclerosis predicted CEP (HR = 1.5, P < .05) but not CV death (HR = 1.4, NS) independently of logUACR (HR = 1.2, P = .09 and HR = 1.94, P < .05). CONCLUSIONS: In hypertensive patients with electrocardiographic LV hypertrophy, AV sclerosis predicted CEP but not CV death independently of UACR after adjusting for CV risk factors and treatment allocation, indicating that AV sclerosis and UACR might be markers of different aspects of the atherosclerotic process.

Aged↗
PubMed2005

Left atrial systolic force and cardiovascular outcome. The Strong Heart Study.

BACKGROUND: The force needed to fill the left ventricle (LV) in late diastole (left atrial systolic force [LASF]) is abnormal in diseased hearts. The goal of this study was to determine whether LASF adds to prognostic prediction of other markers of preclinical cardiovascular disease in a population with a high prevalence of hypertension and diabetes. METHODS: Doppler echocardiography was performed on 2808 participants of the Strong Heart Study (age 59.3 +/- 8.0 years, 62.5% women, 43.0% hypertensive, 46.7% diabetic, and 54.1% obese) without valvular abnormalities or previous cardiovascular events. The LASF was estimated from mitral orifice area and mitral peak A velocity. RESULTS: The LASF was correlated with older age, higher BP, body mass index, creatinine, serum glucose, insulin levels, and heart rate. After controlling for clinical covariates, LASF was independently associated with higher LV dimensions, LV mass, stroke volume, and cardiac output (all P < .01). In Cox regression analysis, greater LASF was associated with a higher rate of CV events (HR = 1.033, 95% CI = 1.005 to 1.061; P = .021), independently of demographic characteristics, risk factors, LV geometry, and transmitral diastolic pattern. CONCLUSIONS: In a population-based sample of middle-aged and elderly adults with a high prevalence of hypertension and diabetes and without prevalent cardiovascular disease, LASF was associated with geometric changes of the heart and with increased rate of combined fatal and nonfatal cardiovascular events.

Atrial Function, Left↗
PubMed2005

Losartan but not atenolol reduce carotid artery hypertrophy in essential hypertension. A LIFE substudy.

BACKGROUND: We wanted to investigate whether treatment with losartan, an angiotensin II receptor blocker, induced regression of carotid artery hypertrophy as compared to the beta-receptor blocker, atenolol. METHODS: In 45 patients recruited for the LIFE Study with stage II-III hypertension and ECG left ventricular (LV) hypertrophy, we measured blood pressure, intima-media thickness (IMT) and lumen in the common carotid arteries by ultrasound, and minimal forearm vascular resistance (MFVR) by plethysmography, after 2 weeks of placebo treatment and after 1, 2 and 3 years of anti-hypertensive treatment with either atenolol- or losartan-based regimens. We measured the same parameters in 26 normal subjects matched for age and gender. RESULTS: The patients had as compared to normotensive controls higher IMT (0.87 vs 0.76 mm, p = 0.001) and intima-media cross-sectional area (IMA) (19.7 vs 15.5 mm2, p<0.001). Systolic and diastolic blood pressures were reduced to the same degree in patients treated with losartan as compared to atenolol. However, IMA decreased significantly only in patients treated with losartan (19.2 vs 17.6 mm2, p = 0.001) and the average relative decrease in IMA during the 3 years of treatment was significantly higher in patients treated with losartan as compared to atenolol (-7.4 vs -2.0%, p<0.05). CONCLUSION: Patients with hypertension and LV hypertrophy had hypertrophy of the common carotid arteries. Losartan, but not atenolol, induced regression of this hypertrophy. Because carotid artery hypertrophy has been associated with strokes, our findings may explain the lower incidence of strokes in the LIFE study in patients treated with losartan as compared to atenolol.

Aged↗
PubMed2005

Body composition and fat distribution influence systemic hemodynamics in the absence of obesity: the HyperGEN Study.

BACKGROUND: We have shown that increased cardiac output is related to both fat-free mass and fat mass in obesity. OBJECTIVE: We studied the association of body fat distribution and body composition with flow-resistance relations in overweight. DESIGN: We studied 521 overweight, nonobese participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study-a component of the National Heart, Lung, and Blood Institute Family Blood Pressure Program, designed to assess the genetic basis of hypertension. Participants had normal ventricular function and no cardiovascular disease: 261 with central fat distribution (CFD) (waist girth >88 cm in women and >102 cm in men) and 260 with peripheral fat distribution (PFD). Fat-free mass (FFM) and fat mass (FM) were measured by bioelectric impedance. Body composition was estimated as FM/FFM. Echocardiographic stroke volume (SV) and cardiac output (CO) were measured. RESULTS: Hypertension was present in 73% of the subjects with PFD and in 78% with CFD. Overweight with CFD was associated with greater FM/FFM in both normotensive and hypertensive participants. After FFM, age, sex, and race were controlled for, SV and CO were higher in subjects overweight with CFD than in those with PFD, whereas peripheral resistance was not significantly different. Differences in CO between CFD and PFD were reduced after further adjustment for FM. After the covariates were controlled for, hypertensive subjects had higher peripheral resistance and lower arterial compliance than did normotensive participants, but cardiac output was not significantly different. CONCLUSION: CFD is associated with more severe abnormalities in body composition and with higher CO independently of FFM in overweight, nonobese subjects.

Adipose Tissue↗
PubMed2005

Aortic valve sclerosis is associated with preclinical cardiovascular disease in hypertensive adults: the Hypertension Genetic Epidemiology Network study.

RATIONALE: Aortic valve sclerosis (AVS) has been associated with atherosclerosis and increased all-cause and cardiovascular death. However, whether AVS is associated with preclinical cardiovascular disease among adults at high risk because of hypertension has not been determined in a population-based sample. METHODS AND RESULTS: Clinical and echocardiographic parameters were measured in 1624 hypertensive participants (54 +/- 11 years, 65% women, 63% black, 17% diabetic, 19% smokers) without significant valvular or cardiovascular diseases in the population-based Hypertension Genetic Epidemiology Network study. The 152 participants with AVS (9.4%), compared with participants without AVS, were older, more often white, male, treated for hypertension or hypercholesteromia (all P < 0.05) and had longer duration and worse hypertension, but did not differ in diabetes status, smoking or fenfluramine use. Adjusting for age, gender and race, the AVS group had higher total cholesterol/high-density lipoprotein-cholesterol (P < 0.05). Controlling for age, gender, race and other clinical covariates, AVS was independently associated with higher septal, posterior and relative wall thicknesses, isovolumic relaxation time and left atrial diameter, and with mild aortic regurgitation and mitral annular calcification (all P < 0.05). CONCLUSIONS: In a population-based sample of hypertensive adults, AVS was prevalent (9.4%) and associated with a proatherogenic clinical profile and abnormal left ventricular geometry and filling, increased left atrial size and mitral annular calcification, which may contribute to the adverse prognosis associated with AVS.

Adult↗