ABSTRACT
BACKGROUND: Although gender-specific criteria are common for defining cardiac traits such as left ventricular hypertrophy, left ventricular ejection fraction (LVEF) thresholds widely used in clinical practice have traditionally been the same for women and men, perhaps because it remains uncertain whether there is a systematic difference in LVEF between genders. METHODS AND RESULTS: Using cardiac magnetic resonance imaging in a probability-based sample of Dallas County residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in women and men. The association of gender with stroke volume independent of end-diastolic volume (EDV) or other potential confounders was assessed by multivariable analysis. Gender-specific thresholds for a low LVEF were defined at the 2.5th percentile in women and men from a healthy reference subpopulation. The median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%, 79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and end-systolic volume indexed to body surface area were smaller in women than in men (P<0.001 for both). Gender remained significantly associated with stroke volume, independent of EDV and other potential confounders in multivariable analysis. A low LVEF was defined as below 61% in women and below 55% in men. CONCLUSIONS: Women have a higher LVEF than men in the general population, secondary to a higher stroke volume for a given EDV independent of known potential confounders.
Subject(s)
Hypertrophy, Left Ventricular/epidemiology , Stroke Volume , Adult , Aged , Body Mass Index , Female , Humans , Hypertrophy, Left Ventricular/etiology , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Myocardial Contraction , Risk Factors , Sex Factors , Texas/epidemiologyABSTRACT
BACKGROUND: The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass. METHODS AND RESULTS: Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels. CONCLUSIONS: In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.
Subject(s)
Body Composition , Body Weight , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Absorptiometry, Photon , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged , Obesity/blood , TexasABSTRACT
BACKGROUND: The prognostic implications of low QRS voltage on the electrocardiogram (ECG) in heart failure (HF) are not well characterized. METHODS: We manually measured and summed the QRS voltage in all 12 leads of the ECG (sumQRS) in two cohorts: (1) 415 patients with a low left ventricular ejection fraction followed up in a HF clinic ("clinic cohort") and (2) 100 subjects with advanced HF who had an ECG within 1 year preceding cardiac transplantation ("pretransplant cohort"). Low voltage was defined as the lowest quartile of the clinic cohort (sumQRS <12 mV) and its prevalence was compared in the two cohorts. The associations of low voltage with 1-year outcomes were assessed in the clinic cohort. RESULTS: In the clinic cohort, the frequency of low voltage was higher in New York Heart Association class 4 versus class 1-3 patients (34% vs 22% respectively, P = .04). The frequency of low voltage in the pretransplant cohort (47%) was twice that of the clinic cohort (24%, P < .001). After 1 year of follow-up in the clinic cohort, low ECG voltage was associated with a higher rate of death (14% vs 5%, P = .008) and the composite end point of death or HF hospitalization (35% vs 20%, P = .004). These associations persisted in multivariable analyses adjusting for important confounders. CONCLUSIONS: Low ECG voltage is a marker of the severity of HF and is a risk factor for adverse outcomes in patients with systolic HF at 1 year.
Subject(s)
Electrocardiography , Heart Failure/etiology , Ventricular Dysfunction, Left/complications , Adult , Female , Heart Failure/epidemiology , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , SystoleABSTRACT
In patients who have ST-segment elevation myocardial infarction (STEMI), a patent infarct-related artery on the initial angiogram is associated with improved clinical outcomes, including decreased mortality. The present study assessed the influence of administering aspirin, beta blockers, statins, and angiotensin-converting enzyme inhibitors before STEMI on infarct-related artery patency. Our data demonstrate that patients who have STEMI and receive these medications on an outpatient basis before the event have a higher likelihood of having a patent infarct-related artery compared with patients who do not receive these medications. Further, our data demonstrate a graded association according to the number of such medications being administered: the likelihood of a patent infarct-related artery increased to >50% as the number of these medications increased.
Subject(s)
Coronary Vessels/physiopathology , Myocardial Infarction/drug therapy , Myocardial Infarction/physiopathology , Vascular Patency/physiology , Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Aspirin/therapeutic use , Coronary Angiography , Coronary Artery Disease/physiopathology , Electrocardiography , Female , Heart Failure/physiopathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypertension/physiopathology , Logistic Models , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Platelet Aggregation Inhibitors/therapeutic use , Troponin/bloodABSTRACT
Elevated plasma levels of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are seen in the setting of cardiac ischemia and are associated with adverse outcomes in patients with coronary artery disease. The mechanisms leading to natriuretic peptide elevation in patients with coronary artery disease, including the contribution of coronary atherosclerosis itself, have not been fully elucidated. Measurement of NT-pro-BNP, electron beam computed tomography, and cardiac magnetic resonance imaging were performed in 2,445 subjects from the Dallas Heart Study who were free of heart failure and renal insufficiency. Electron beam computed tomography-determined coronary artery calcium scores were categorized as none (<10), mild (> or =10 to <100), moderate (> or =100 to <400), and severe (> or =400). NT-pro-BNP levels increased significantly across increasing coronary artery calcium score categories (p <0.0001 for trend). In multivariate models adjusted for age, gender, race, body mass index, hypertension, history of myocardial infarction, angina, angiotensin-converting enzyme inhibitor use, beta-blocker use, left ventricular (LV) ejection fraction, and LV mass, higher coronary artery calcium scores remained independently associated with higher log NT-pro-BNP levels (p = 0.03). This association persisted in similar models excluding patients with low LV ejection fractions, LV hypertrophy, angina pectoris, and a history of myocardial infarction. In conclusion, these findings support the hypothesis that coronary atherosclerosis may directly influence the activation of the cardiac neurohormonal system.
Subject(s)
Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Protein Precursors/blood , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Biomarkers/blood , Coronary Artery Disease/ethnology , Female , Humans , Male , Middle Aged , Prognosis , Risk Factors , Texas/ethnologyABSTRACT
BACKGROUND: Electrocardiographic imaging (ECGI) is a method for noninvasive epicardial electrophysiologic mapping. ECGI previously has been used to characterize the electrophysiologic substrate and electrical synchrony in a very heterogeneous group of patients with varying degrees of coronary disease and ischemic cardiomyopathy. OBJECTIVE: The purpose of this study was to characterize the left ventricular electrophysiologic substrate and electrical dyssynchrony using ECGI in a homogeneous group of nonischemic cardiomyopathy patients who were previously implanted with a cardiac resynchronization therapy (CRT) device. METHODS: ECGI was performed during different rhythms in 25 patients by programming their devices to biventricular pacing, single-chamber (left ventricular or right ventricular) pacing, and native rhythm. The electrical dyssynchrony index (ED) was computed as the standard deviation of activation times at 500 sites on the LV epicardium. RESULTS: In all patients, native rhythm activation was characterized by lines of conduction block in a region with steep activation-recovery interval (ARI) gradients between the epicardial aspect of the septum and LV lateral wall. A native QRS duration (QRSd) >130 ms was associated with high ED (≥30 ms), whereas QRSd <130 ms was associated with minimal (25 ms) to large (40 ms) ED. CRT responders had very high dyssynchrony (ED = 35.5 ± 3.9 ms) in native rhythm, which was significantly lowered (ED = 23.2 ± 4.4 ms) during CRT. All four nonresponders in the study did not show significant difference in ED between native and CRT rhythms. CONCLUSION: The electrophysiologic substrate in nonischemic cardiomyopathy is consistent among all patients, with steep ARI gradients co-localizing with conduction block lines between the epicardial aspect of the septum and the LV lateral wall. QRSd wider than 130 ms is indicative of substantial LV electrical dyssynchrony; however, among patients with QRSd <130 ms, LV dyssynchrony may vary widely.
Subject(s)
Body Surface Potential Mapping , Cardiac Resynchronization Therapy , Electrophysiologic Techniques, Cardiac , Heart Failure/physiopathology , Heart Failure/therapy , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle AgedABSTRACT
To elucidate mechanisms by which left ventricular (LV) hypertrophy (LVH) increases the risk of atherosclerotic heart disease, we sought to determine whether LVH is independently associated with coronary artery calcium (CAC) and serum C-reactive protein (CRP) levels in the general population. The Dallas Heart Study is a population-based sample in which 2633 individuals underwent cardiac MRI to measure LV structure, electron beam CT to measure CAC, and measurement of plasma CRP. We used univariate and multivariable analyses to determine whether LV mass and markers of concentric LV hypertrophy or dilation were associated with CAC and CRP. Increasing quartiles of LV mass indexed to fat-free mass, LV wall thickness, and concentricity, but not LV volume, were associated with CAC in both men and women (P<0.001). After adjustment for traditional cardiovascular risk factors and statin use, LV wall thickness and concentricity remained associated with CAC in linear regression (P<0.001 for each). These associations were particularly robust in blacks. LV wall thickness and concentricity were also associated with elevated CRP levels (P=0.001 for both) in gender-stratified univariate analyses, although these associations did not persist in multivariable analysis. In conclusion, concentric LVH is an independent risk factor for subclinical atherosclerosis. LVH is also associated with an inflammatory state as reflected in elevated CRP levels, although this relationship appears to be mediated by comorbid conditions. These data likely explain in part why individuals with LVH are at increased risk for myocardial infarction.
Subject(s)
Coronary Artery Disease/etiology , Hypertrophy, Left Ventricular/complications , Inflammation/etiology , Adult , Blood Pressure/physiology , C-Reactive Protein/metabolism , Calcium/metabolism , Cohort Studies , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Coronary Vessels/metabolism , Cross-Sectional Studies , Female , Humans , Hypertrophy, Left Ventricular/pathology , Inflammation/metabolism , Inflammation/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Risk Factors , Texas , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: Higher C-reactive protein (CRP) levels in women compared with men may reflect sex differences in the relationship between obesity and inflammation. We evaluated how the adipokine leptin influenced these relationships. METHODS AND RESULTS: Dual energy X-ray absorptometry measurements of fat mass and plasma levels of leptin and CRP were measured in 1188 women and 1102 men from the Dallas Heart Study. Analyses were stratified by sex and a leptin/percent fat index was created to evaluate the association between leptin and CRP independent of fat mass. Women had higher body mass index, percent fat mass, and plasma levels of CRP and leptin. CRP levels correlated with leptin levels in both women (Spearman rho=0.48, p<0.0001) and in men (rho=0.27, p<0.0001). In multivariable models adjusting for confounders including total fat mass, leptin/percent fat index remained significantly associated with logCRP in women (p=0.005), but not in men (p=0.95). A significant interaction was observed between sex and leptin levels on CRP (p(interaction)=0.03). CONCLUSION: Leptin was associated with CRP independent of other measures of obesity in women, but not in men. These findings suggest that sex differences in CRP may reflect sex-related differences in the inflammatory responses to obesity, and may in part, be mediated by leptin.
Subject(s)
C-Reactive Protein/analysis , Leptin/blood , Obesity/blood , Adult , Body Composition , Body Mass Index , Cross-Sectional Studies , Female , Humans , Inflammation/blood , Male , Middle Aged , Sex Factors , Statistics as TopicABSTRACT
Sequence variations in the human alpha2 adrenergic receptor genes (ADRA2A and ADRA2C) have been implicated as a cause of hypertension in blacks. Although certain alleles are selectively enriched in blacks, their association with hypertension is based on small convenience samples and has not been evaluated in larger populations. From a stratified random population sample of 3398 individuals (52% blacks), we obtained DNA samples together with an in-home health interview, 10 in-home measurements of blood pressure, and cardiac MRI. We tested for associations among hypertension, untreated blood pressure, and parameters of hypertensive heart disease with 2 alleles, a DraI restriction fragment length polymorphism in the ADRA2A gene and a deletion of residues 322 to 325 in the ADRA2C gene. Although both alleles were selectively enriched in this black population, we found no association of either allele with hypertension, untreated blood pressure, or any of the cardiac function parameters. In a logistic model that controlled for age, body mass index, diabetes, and smoking, the adjusted odds ratio (OR) for hypertension was 1.0 (95% CI, 0.8 to 1.2), and 1.0 (95% CI, 0.9 to 1.2) for ADRA2A and ADRA2C variant alleles. In subjects not receiving prescription blood pressure medication, neither of these alleles, alone or in combination, was predictive of blood pressure, heart rate, left ventricular mass, cardiac output, systemic vascular resistance, or aortic compliance. Both the DraI restriction fragment length polymorphism in ADRA2A and the ADRA2C (Del 322 to 325) can be excluded as major candidate alleles for hypertension in blacks.